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</div>
|
||
</div>
|
||
|
||
|
||
</form>
|
||
|
||
|
||
<div id="article-page-header">
|
||
<div id="article-top-actions-bar" class="article-top-actions-bar">
|
||
<div class="inner-wrap">
|
||
<div class="actions-container">
|
||
<div class="return-to-search">
|
||
|
||
|
||
</div>
|
||
|
||
<div class="multiple-results-actions " role="region" aria-label="save, email, send to">
|
||
<button id="save-results-panel-trigger"
|
||
type="button"
|
||
class="save-results save-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="save-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="open">
|
||
Save
|
||
</button><button id="email-results-panel-trigger"
|
||
type="button"
|
||
class="email-results email-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="email-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="open">
|
||
Email
|
||
</button><div class="more-actions dropdown-block"><button id="more-actions-trigger"
|
||
type="button"
|
||
class="trigger more-actions-trigger"
|
||
ref="linksrc=show_moreactions_btn"
|
||
aria-label="Send to"
|
||
aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link "
|
||
href="#"
|
||
role="button"
|
||
data-ga-category="save_share"
|
||
data-ga-action="clipboard"
|
||
data-ga-label="send">
|
||
Clipboard
|
||
</a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F36211450%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F36211450%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region">
|
||
<button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog">
|
||
<span class="button-label">Display options</span>
|
||
</button>
|
||
|
||
<div class="dropdown" hidden>
|
||
<div class="title">
|
||
Display options
|
||
</div>
|
||
|
||
<div class="content">
|
||
|
||
<div class="format-container">
|
||
<span class="option-label">
|
||
Format
|
||
</span>
|
||
<select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format">
|
||
<option value="abstract">Abstract</option>
|
||
|
||
<option value="pubmed">PubMed</option>
|
||
|
||
<option value="pmid">PMID</option>
|
||
|
||
</select>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="IpAHyZxWRYm8yNS7meEZlQRZx63Ii4CVZckMbP0irz9CseYXZxh1PYnD5aLUbFaf">
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="article-panels-container" class="article-panels-container">
|
||
<div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Save citation to file
|
||
</h2>
|
||
<form id="save-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="IpAHyZxWRYm8yNS7meEZlQRZx63Ii4CVZckMbP0irz9CseYXZxh1PYnD5aLUbFaf">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="save-action-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="save-action-format" name="results-format" class="action-panel-selector">
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="pubmed-text">PubMed</option>
|
||
<option value="pmid">PMID</option>
|
||
<option value="abstract">Abstract (text)</option>
|
||
<option value="csv">CSV</option>
|
||
</select>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Save citations to file' panel"
|
||
ref="linksrc=close_save_panel"
|
||
aria-controls="save-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="email-action-panel"
|
||
class="email-action-panel action-panel"
|
||
aria-hidden="true"
|
||
data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback"
|
||
data-recaptcha-enabled="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Email citation
|
||
</h2>
|
||
<form id="email-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/send-email/"
|
||
data-by-search-action="/results-export-email-by-search-data/"
|
||
data-by-ids-action="/send-email/"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post"
|
||
method="post"
|
||
>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="IpAHyZxWRYm8yNS7meEZlQRZx63Ii4CVZckMbP0irz9CseYXZxh1PYnD5aLUbFaf">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<span class="action-panel-label">
|
||
Subject:
|
||
</span>
|
||
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 36211450 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 36211450"/>
|
||
<input type="hidden" name="email-subject-hash" value="7c3d79f79610d77270d8cba71cf25caa9cfc6b047940ab259700ae66cb4eddc2"/>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-to" class="action-panel-label required-field-asterisk">
|
||
To:
|
||
</label>
|
||
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-from" class="action-panel-label">
|
||
From:
|
||
</label>
|
||
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
|
||
</div>
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-citation-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
|
||
<option selected="selected" value="summary">Summary</option>
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="abstract">Abstract</option>
|
||
<option value="abstract-text">Abstract (text)</option>
|
||
|
||
</select>
|
||
</div>
|
||
<div class="include-supplemental-container">
|
||
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
|
||
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="form-field recaptcha ">
|
||
|
||
|
||
|
||
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
|
||
|
||
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="send">
|
||
Send email
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Email citations' panel"
|
||
ref="linksrc=close_email_panel"
|
||
aria-controls="email-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
<input type="hidden" name="email-search-details" value="" />
|
||
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="collections-action-panel"
|
||
class="collections-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-collections-open-panel-enabled="false"
|
||
data-collections-open-panel-url-hash="#open-collections-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to Collections
|
||
</h3>
|
||
|
||
|
||
<form id="collections-action-panel-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-add-to-collection-max-amount="1000"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="IpAHyZxWRYm8yNS7meEZlQRZx63Ii4CVZckMbP0irz9CseYXZxh1PYnD5aLUbFaf">
|
||
|
||
|
||
|
||
<div class="choice-group" role="radiogroup">
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_new">
|
||
<label for="collections-action-panel-new">Create a new collection</label>
|
||
</li>
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_existing">
|
||
<label for="collections-action-panel-existing">Add to an existing collection</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
|
||
<div class="controls-wrapper">
|
||
<div class="action-panel-control-wrap new-collections-controls">
|
||
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label>
|
||
<input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-panel-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="save_share"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection">
|
||
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div>
|
||
</div>
|
||
<div class="action-panel-control-wrap existing-collections-controls">
|
||
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label>
|
||
<select id="collections-action-panel-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="save_share"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
|
||
</select>
|
||
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="add">
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="bibliography-action-panel"
|
||
class="bibliography-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-bibliography-open-panel-enabled="false"
|
||
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to My Bibliography
|
||
</h3>
|
||
<form id="bibliography-action-panel-form"
|
||
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-add-to-bibliography-max-amount="100"
|
||
data-add-to-bibliography-batch-size="10"
|
||
data-bibliography-delegates-url="/list-bibliography-delegates/"
|
||
data-add-to-bibliography-url="/add-to-bibliography/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="IpAHyZxWRYm8yNS7meEZlQRZx63Ii4CVZckMbP0irz9CseYXZxh1PYnD5aLUbFaf">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap bibliographies-controls">
|
||
<div class="choice-group">
|
||
<ul class="bibliographies-action-add radio-group-items">
|
||
<li>
|
||
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
|
||
<label for="my-bibliography">My Bibliography</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your delegates due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore>
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to bibliography' panel"
|
||
ref="linksrc=close_bibliography_panel"
|
||
aria-controls="bibliography-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="mybib"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
|
||
data-saved-search-open-panel-enabled="false"
|
||
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your saved search
|
||
</h2>
|
||
|
||
<form id="saved-search-action-panel-form"
|
||
class="saved-search-action-panel-form action-panel-content action-form"
|
||
data-create-saved-search-url="/create-saved-search/"
|
||
data-try-search-terms-url="/try-search-term/"
|
||
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="IpAHyZxWRYm8yNS7meEZlQRZx63Ii4CVZckMbP0irz9CseYXZxh1PYnD5aLUbFaf">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
|
||
Name of saved search:
|
||
</label>
|
||
<input maxlength="200"
|
||
type="text"
|
||
name="saved-search-name"
|
||
id="saved-search-name"
|
||
class="saved-search-name"
|
||
value=""
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
|
||
Search terms:
|
||
</label>
|
||
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
|
||
</div>
|
||
<div class="test-search-term-wrap">
|
||
<a href="#" class="try-search-term">Test search terms</a>
|
||
</div>
|
||
<div class="choice-group action-panel-extra-margin-top">
|
||
<span class="action-panel-label" id="fieldset-label">
|
||
Would you like email updates of new search results?
|
||
</span>
|
||
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
|
||
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
|
||
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
|
||
</li>
|
||
<li>
|
||
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
|
||
<label for="saved-search-alert-no" class="action-panel-label">No</label>
|
||
</li>
|
||
</ul>
|
||
</fieldset>
|
||
</div>
|
||
|
||
<div class="alert-schedule-wrap">
|
||
<div class="action-panel-control-wrap">
|
||
<label class="action-panel-label">
|
||
Email:
|
||
</label>
|
||
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
|
||
</div>
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="saved-search-frequency" class="action-panel-label">
|
||
Frequency:
|
||
</label>
|
||
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
|
||
<option value="monthly">Monthly</option>
|
||
<option value="weekly">Weekly</option>
|
||
<option value="daily">Daily</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-monthly-additional">
|
||
<label for="saved-search-monthly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
|
||
<option value="Sunday">The first Sunday</option>
|
||
<option value="Monday">The first Monday</option>
|
||
<option value="Tuesday">The first Tuesday</option>
|
||
<option value="Wednesday">The first Wednesday</option>
|
||
<option value="Thursday">The first Thursday</option>
|
||
<option value="Friday">The first Friday</option>
|
||
<option value="Saturday">The first Saturday</option>
|
||
<option value="day">The first day</option>
|
||
<option value="weekday">The first weekday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-weekly-additional">
|
||
<label for="saved-search-weekly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
|
||
<option value="Sunday">Sunday</option>
|
||
<option value="Monday">Monday</option>
|
||
<option value="Tuesday">Tuesday</option>
|
||
<option value="Wednesday">Wednesday</option>
|
||
<option value="Thursday">Thursday</option>
|
||
<option value="Friday">Friday</option>
|
||
<option value="Saturday">Saturday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-report" class="action-panel-label">
|
||
Report format:
|
||
</label>
|
||
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
|
||
<option value="DocSum">Summary</option>
|
||
<option value="DocSumText">Summary (text)</option>
|
||
<option value="Abstract">Abstract</option>
|
||
<option value="AbstractText">Abstract (text)</option>
|
||
<option value="MEDLINE">PubMed</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-amount" class="action-panel-label">
|
||
Send at most:
|
||
</label>
|
||
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
|
||
<option value="1">1 item</option>
|
||
<option value="5" selected>5 items</option>
|
||
<option value="10">10 items</option>
|
||
<option value="20">20 items</option>
|
||
<option value="50">50 items</option>
|
||
<option value="100">100 items</option>
|
||
<option value="200">200 items</option>
|
||
</select>
|
||
</div>
|
||
<div>
|
||
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
|
||
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
|
||
Send even when there aren't any new results
|
||
</label>
|
||
</div>
|
||
<div class="action-panel-control-wrap option-text-in-email-wrap">
|
||
<label for="saved-search-email-text" class="action-panel-label">
|
||
Optional text in email:
|
||
</label>
|
||
<textarea name="saved-search-email-text"
|
||
id="saved-search-email-text"
|
||
class="saved-search-email-text"></textarea>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Save
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your saved search' panel"
|
||
ref="linksrc=close_saved_search_panel"
|
||
aria-controls="saved-search-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Create a file for external citation management software
|
||
</h2>
|
||
<form id="citation-manager-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="IpAHyZxWRYm8yNS7meEZlQRZx63Ii4CVZckMbP0irz9CseYXZxh1PYnD5aLUbFaf">
|
||
|
||
|
||
|
||
<input name="results-format" type="hidden" value="pubmed"/>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Send citations to citation manager' panel"
|
||
ref="linksrc=close_citation_manager_panel"
|
||
aria-controls="citation-manager-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your RSS Feed
|
||
</h2>
|
||
|
||
<form id="rss-action-panel-form"
|
||
class="rss-action-panel-form action-panel-content action-form"
|
||
data-create-rss-feed-url="/create-rss-feed-url/"
|
||
data-search-form-term-value="">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="IpAHyZxWRYm8yNS7meEZlQRZx63Ii4CVZckMbP0irz9CseYXZxh1PYnD5aLUbFaf">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="rss-name" class="action-panel-label required-field-asterisk">
|
||
Name of RSS Feed:
|
||
</label>
|
||
<input maxlength="200"
|
||
placeholder="Name"
|
||
type="text"
|
||
name="rss-name"
|
||
id="rss-name"
|
||
class="rss-name"
|
||
value=''
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="rss-limit-wrap">
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="rss-limit" class="action-panel-label">
|
||
Number of items displayed:
|
||
</label>
|
||
<select id="rss-limit" class="no-border-panel-selector rss-limit">
|
||
<option value="5">5</option>
|
||
<option value="10">10</option>
|
||
<option value="15" selected="selected">15</option>
|
||
<option value="20">20</option>
|
||
<option value="50">50</option>
|
||
<option value="100">100</option>
|
||
</select>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Creating..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Create RSS
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your RSS' panel"
|
||
ref="linksrc=close_rss_panel"
|
||
aria-controls="rss-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap rss-link-copy-wrap">
|
||
<label for="rss-link" class="usa-sr-only">RSS Link</label>
|
||
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
|
||
<button
|
||
type="button"
|
||
disabled
|
||
class="rss-link-copy-button disabled"
|
||
data-ga-category="save_share"
|
||
data-ga-action="rss"
|
||
data-ga-label="copy">
|
||
Copy
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="article-page" id="article-page" data-article-pmid="36211450">
|
||
<aside class="page-sidebar">
|
||
<div class="inner-wrap">
|
||
|
||
<div class="full-text-links">
|
||
<div class="full-view">
|
||
<h3 class="title">
|
||
Full text links
|
||
</h3>
|
||
<div class="full-text-links-list">
|
||
<a class="link-item
|
||
|
||
dialog-focus"
|
||
href="https://doi.org/10.3389/fcell.2022.945586"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=6956&itool=Abstract-def&log$=linkouticon&uid=36211450&db=pubmed&nlmid=101630250"
|
||
title="See full text options at Frontiers Media SA"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="Frontiers Media SA"
|
||
data-ga-label="36211450"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.frontiersin.org-alerts-logo-PubMed.png" alt="Frontiers Media SA full text link"><span class="text">
|
||
|
||
Frontiers Media SA
|
||
|
||
</span></a><a class="link-item
|
||
pmc
|
||
"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/36211450/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=36211450&db=pubmed&nlmid=101630250"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="36211450"
|
||
><span class="text">
|
||
|
||
Free PMC article
|
||
|
||
</span></a>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="short-view">
|
||
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
|
||
Full text links
|
||
</a>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
|
||
aria-label="Open dialog with citation text in different styles"
|
||
data-ga-category="save_share"
|
||
data-ga-action="cite"
|
||
data-ga-label="open"
|
||
data-all-citations-url="/36211450/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/36211450/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="36211450" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
|
||
aria-label="Save article in MyNCBI collections."
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_button"
|
||
data-collections-open-dialog-enabled="false"
|
||
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F36211450%2F%23open-collections-dialog"
|
||
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
|
||
class="dialog collections-dialog"
|
||
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="IpAHyZxWRYm8yNS7meEZlQRZx63Ii4CVZckMbP0irz9CseYXZxh1PYnD5aLUbFaf"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
|
||
id="collections-action-dialog-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
|
||
id="collections-action-dialog-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label><input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-dialog-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label><select id="collections-action-dialog-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="add">
|
||
Add
|
||
</button><button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger"
|
||
title="Open dialog with more actions to take"
|
||
ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region"><button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title">
|
||
Display options
|
||
</div><div class="content"><div class="format-container"><span class="option-label">
|
||
Format
|
||
</span><select name="format" data-initial-value="abstract" aria-label="Display format" id="sidebar-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div>
|
||
|
||
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Bioinformatic analysis of the <i>LCN2-SLC22A17-MMP9</i> network in cancer: The role of DNA methylation in the modulation of tumor microenvironment
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Several features of cancer cells such as proliferation, invasion, metastatic spreading, and drug resistance are affected by their interaction with several tumor microenvironment (TME) components, including neutrophil gelatinase-associated lipocalin (NGAL), solute carrier family 22 member 17 (SLC22A17), and matrix metallopeptidase 9 (MMP9). These molecules play a key role in tumor growth, invasion, and iron-dependent metabolism of cancer cells. However, the precise epigenetic mechanisms underlying the gene regulation of <i>Lipocalin 2</i> (<i>LCN2</i>), <i>SLC22A17</i>, and <i>MMP9</i> in cancer still remain unclear. To this purpose, computational analysis was performed on TCGA and GTEx datasets to evaluate the expression and DNA methylation status of <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> genes in different tumor types. Correlation analysis between gene/isoforms expression and DNA methylation levels of <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> was performed to investigate the role of DNA methylation in the modulation of these genes. Protein network analysis was carried out using reverse phase protein arrays (RPPA) data to identify protein-protein interactions of the <i>LCN2</i>-<i>SLC22A17</i>-<i>MMP9</i> network. Furthermore, survival analysis was performed according to gene expression and DNA methylation levels. Our results demonstrated that <i>LCN2</i> and <i>MMP9</i> were mainly upregulated in most tumor types, whereas <i>SLC22A17</i> was largely downregulated, representing a specific hallmark signature for all gastrointestinal tumors. Notably, the expression of <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> genes was negatively affected by promoter methylation. Conversely, intragenic hypermethylation was associated with the overexpression of <i>SLC22A17</i> and <i>MMP9</i> genes. Protein network analysis highlighted the role of the <i>LCN2</i>-<i>SLC22A17</i>-<i>MMP9</i> network in TME by the interaction with fibronectin 1 and claudin 7, especially in rectal tumors. Moreover, the impact of expression and methylation status of <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> on overall survival and progression free interval was tumor type-dependent. Overall, our analyses provide a detailed overview of the expression and methylation status of <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> in all TCGA tumors, indicating that the <i>LCN2-SLC22A17-MMP9</i> network was strictly regulated by DNA methylation within TME. Our findings pave the way for the identification of novel DNA methylation hotspots with diagnostic and prognostic values and suitable for epi-drug targeting.
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<strong class="sub-title">
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Keywords:
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</strong>
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DNA methylation; LCN2; MMP9; SLC22A17; bioinformatic; cancer; ferroptosis; gene expression.
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<p class="copyright" id="copyright">
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Copyright © 2022 Candido, Tomasello, Lavoro, Falzone, Gattuso, Russo, Paratore, McCubrey and Libra.
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<a href="/disclaimer/" target="_blank" data-ga-category="literature_resources"
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data-ga-action="disclaimer_link" data-ga-label="under_abstract">PubMed Disclaimer</a>
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<div class="conflict-of-interest" id="conflict-of-interest">
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Conflict of interest statement
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<div class="statement">
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<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
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<div class="figure-caption-contents"><p> Differential analysis of <i> LCN2 </i> ,… </p></div>
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<div class="figure-caption-contents"><p> Differential analysis of <i> LCN2 </i> , <i> SLC22A17 </i> , and <i> MMP9 </i> expression levels in TCGA… </p></div>
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FIGURE 1
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<div class="figure-caption-contents">Differential analysis of <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> expression levels in TCGA tumor and GTEx normal samples. <b>(A)</b> Expression levels of <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> genes and isoforms in normal (blue) and tumor samples (red). Fold Change was reported for each comparing group. <b>(B)</b> Distribution of expression median values calculated for the gene and isoforms (empty circles) is shown for each tumor type and matched normal tissues. Black bold labels indicate the <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> gene expression (ENSG), including all spliced transcripts (ENST). Coding isoforms: blue; non-coding isoforms: green; retained intron isoforms: red.</div>
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<div class="figure-caption-contents"><p> Heatmap of median expression levels… </p></div>
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<p> FIGURE 2 </p>
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<div class="figure-caption-contents"><p> Heatmap of median expression levels for <i> LCN2 </i> , <i> SLC22A17 </i> , and <i> MMP9 </i> genes… </p></div>
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FIGURE 2
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<div class="figure-caption-contents">Heatmap of median expression levels for <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> genes and isoforms in tumor samples according to interquartile range of normal samples median values. The median values of each tumor type higher than the 3rd quartile <b>(A)</b> or lower than the 1st quartile of normal tissues <b>(B)</b> are reported. The negative median values (lower expression) are shown as blue squares, while positive ones (higher expression) are indicated in red. Black border indicates the median values of each tumor type that are also outliers. Black bold labels indicate the <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> genes (ENSG). Coding ENST isoforms: blue; non-coding ENST isoforms: green; retained intron ENST isoforms: red.</div>
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<div class="figure-caption-contents"><p> Expression and correlation analyses of gene (ENSG) and splicing isoforms (ENST) of LCN2,… </p></div>
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FIGURE 3
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<div class="figure-caption-contents">Expression and correlation analyses of gene (ENSG) and splicing isoforms (ENST) of LCN2, SLC22A17, and MMP9 in normal and tumoral tissues. <b>(A)</b> Percentage of tumor types in which <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> expression levels were up (red) or downregulated (blue) compared to normal tissues. Only tumors showing FC ≥ 1.4 or ≤ −1.4 (<i>p</i> ≤ 0.05) are included in the analysis. <b>(B)</b> Correlation analysis between <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> genes and isoforms expression in normal and tumor samples. Tumor and normal samples were analyzed collectively. Correlation with Pearson’s r ≥ 0.3 or ≤ −0.3 and <i>p</i> ≤ 0.05 were included in the heatmap. Black bold labels indicate the <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> genes (ENSG). Coding ENST isoforms: blue; non-coding ENST isoforms: green; retained intron ENST isoforms: red.</div>
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<div class="figure-caption-contents"><p> Correlation analysis between <i> LCN2 </i> ,… </p></div>
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<div class="figure-caption-contents"><p> Correlation analysis between <i> LCN2 </i> , <i> SLC22A17 </i> , and <i> MMP9 </i> gene/isoforms expression and protein… </p></div>
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FIGURE 4
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<div class="figure-caption-contents">Correlation analysis between <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> gene/isoforms expression and protein levels in PANCAN tumor samples. Correlation with Pearson’s r ≥ 0.3 or ≤ −0.3 and <i>p</i> ≤ 0.05 are included in the heatmap. The average linkage clustering method and Euclidean distance measurement method were applied for grouping similar data in seven representative clusters. Each protein is labeled with three different colors corresponding to 1, 6, and 9 tumor groups (Supplementary Table S6). Black bold labels indicate the <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> genes (ENSG). Coding ENST isoforms: blue; non-coding ENST isoforms: green; retained intron ENST isoforms: red.</div>
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|
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<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-4"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/0f5f57517e25/fcell-10-945586-g005.gif"
|
||
alt="FIGURE 5" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="650">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="520">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 5 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Correlation analysis between <i> LCN2 </i> ,… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 5 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Correlation analysis between <i> LCN2 </i> , <i> SLC22A17 </i> , and <i> MMP9 </i> gene expression and protein… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 5
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">Correlation analysis between <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> gene expression and protein levels in tumor types. Protein-gene interaction showing correlation (Pearson’s r ≥ 0.3 or ≤ −0.3; <i>p</i> ≤ 0.05) in at least five tumor types are reported. The concordance among Pearson’s values was defined as the degree of agreement among the correlation sign. Partial concordance: dotted interaction lines. Total concordance: solid interaction lines. Proteins interacting with two genes are represented in blue, while proteins interacting with all three genes are represented in orange. The network was obtained from Cytoscape 3.8.2 (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://cytoscape.org/">https://cytoscape.org/</ext-link>).</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="5"
|
||
data-label-slug="figure-6">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/724c271ed032/fcell-10-945586-g006.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-5"
|
||
role="button"
|
||
data-image-width="722"
|
||
data-image-height="791"
|
||
data-image-alt="FIGURE 6"
|
||
data-pmc-id="PMC9532607"
|
||
data-figure-id="F6">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-5"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/ad6f760d5f14/fcell-10-945586-g006.gif"
|
||
alt="FIGURE 6" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="722">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="791">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 6 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Correlation and pathway analysis of… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 6 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Correlation and pathway analysis of protein levels analyzed in each tumor type. <b> (A)… </b> </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 6
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">Correlation and pathway analysis of protein levels analyzed in each tumor type. <b>(A)</b> Protein–protein interaction showing correlation (Pearson’s r ≥ 0.3 or ≤ −0.3; <i>p</i> ≤ 0.05) in at least 20 tumor types are represented. The concordance among Pearson’s value means was defined as a degree of agreement among the correlation sign. Partial concordance: dotted interaction lines. Total concordance: solid interaction lines. The network was obtained from Cytoscape 3.8.2 (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://cytoscape.org/">https://cytoscape.org/</ext-link>). <b>(B)</b> STRING network analysis (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://string-db.org/">https://string-db.org/</ext-link>) of selected proteins significantly correlated with each other (Pearson’s r ≥ 0.3 or ≤ −0.3; <i>p</i> ≤ 0.05). Edge thickness indicates the strength of data support. <b>(C)</b> Gene ontology analysis according to STRING algorithms. Strength of functional enrichments and count of proteins in each KEGG pathway are indicated.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item tail"
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="6"
|
||
data-label-slug="figure-7">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/088d4bf366b9/fcell-10-945586-g007.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-6"
|
||
role="button"
|
||
data-image-width="616"
|
||
data-image-height="915"
|
||
data-image-alt="FIGURE 7"
|
||
data-pmc-id="PMC9532607"
|
||
data-figure-id="F7">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-6"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/7958c79768dd/fcell-10-945586-g007.gif"
|
||
alt="FIGURE 7" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="616">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="915">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 7 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> OS and PFI analyses according… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 7 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> OS and PFI analyses according to <i> LCN2 </i> , <i> SCL22A17 </i> , and <i> MMP9 </i> gene… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-6" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 7
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">OS and PFI analyses according to <i>LCN2</i>, <i>SCL22A17</i>, and <i>MMP9</i> gene expression. Volcano plot visualization of tumor types in which <i>LCN2</i>, <i>SCL22A17</i>, and <i>MMP9</i> gene expression affected the patient’s overall survival <b>(A)</b> and progression free interval <b>(B)</b>. The genes showing significant log-rank test (<i>p</i> ≤ 0.05) are represented in red (unfavorable) or in blue (favorable) according to their prognostic significance in each tumor type.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item tail"
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="7"
|
||
data-label-slug="figure-8">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/69b65dda59d4/fcell-10-945586-g008.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-7"
|
||
role="button"
|
||
data-image-width="648"
|
||
data-image-height="1154"
|
||
data-image-alt="FIGURE 8"
|
||
data-pmc-id="PMC9532607"
|
||
data-figure-id="F8">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-7"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/db7a2afc8450/fcell-10-945586-g008.gif"
|
||
alt="FIGURE 8" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="648">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="1154">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 8 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> DNA methylation profiling of <i> LCN2… </i> </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 8 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> DNA methylation profiling of <i> LCN2 </i> , <i> SLC22A17 </i> , and <i> MMP9 </i> in all tumor… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-7" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 8
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">DNA methylation profiling of <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> in all tumor samples. <b>(A–C)</b> For each CG methylation probeset, the mean of methylation beta value is displayed for all tumor types (empty circles). <b>(D)</b> Heatmap showing the tumors in which the mean GC probeset beta value resulted lower (red) or upper (blue) outliers.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item tail"
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="8"
|
||
data-label-slug="figure-9">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/bd0efb6947e0/fcell-10-945586-g009.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-8"
|
||
role="button"
|
||
data-image-width="678"
|
||
data-image-height="489"
|
||
data-image-alt="FIGURE 9"
|
||
data-pmc-id="PMC9532607"
|
||
data-figure-id="F9">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-8"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/f694e7afcc1c/fcell-10-945586-g009.gif"
|
||
alt="FIGURE 9" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="678">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="489">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 9 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Correlation analysis between <i> LCN2 </i> <b> (A)… </b> </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 9 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Correlation analysis between <i> LCN2 </i> <b> (A) </b> , <i> SLC22A17 </i> <b> (B) </b> , and <i> MMP9 </i> <b> (C) </b> gene/isoforms… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-8" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 9
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">Correlation analysis between <i>LCN2</i>
|
||
<b>(A)</b>, <i>SLC22A17</i>
|
||
<b>(B)</b>, and <i>MMP9</i>
|
||
<b>(C)</b> gene/isoforms expression and CG probesets methylation levels in all tumors. Correlation with Pearson’s r ≥ 0.3 or ≤ −0.3 and <i>p</i> ≤ 0.05 were included in the heatmap. Black bold labels indicate the <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> genes (ENSG). Coding ENST isoforms: blue; non-coding ENST isoforms: green; retained intron ENST isoforms: red.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item tail"
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="9"
|
||
data-label-slug="figure-10">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/568d7ceec71b/fcell-10-945586-g010.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-9"
|
||
role="button"
|
||
data-image-width="638"
|
||
data-image-height="760"
|
||
data-image-alt="FIGURE 10"
|
||
data-pmc-id="PMC9532607"
|
||
data-figure-id="F10">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-9"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/723329daee87/fcell-10-945586-g010.gif"
|
||
alt="FIGURE 10" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="638">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="760">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 10 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Correlation analysis between <i> LCN2 </i> gene/isoforms… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 10 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Correlation analysis between <i> LCN2 </i> gene/isoforms expression and relative CG probesets methylation levels in… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-9" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 10
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">Correlation analysis between <i>LCN2</i> gene/isoforms expression and relative CG probesets methylation levels in each tumor type. <b>(A)</b> Volcano plot showing the correlation between CG probesets and gene/isoforms expression of <i>LCN2</i> (Pearson’s r ≥ 0.3 and ≤ −0.3, <i>p</i> ≤ 0.01). The top ten hits (five positive and five negative) based on correlation significance are labeled. Blue dots: negative correlation, red dots: positive correlation. <b>(B)</b> Percentage of tumor types, gene/isoforms and CG probesets showing Pearson’s r ≥ 0.3 and ≤ −0.3 (<i>p</i> ≤ 0.01), separately. No more than ten variables with the highest correlation values are indicated.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item tail"
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="10"
|
||
data-label-slug="figure-11">
|
||
<a class="figure-link"
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/54816549b432/fcell-10-945586-g011.jpg"
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data-image-alt="FIGURE 11"
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data-pmc-id="PMC9532607"
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data-figure-id="F11">
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<img class="figure-thumb" itemprop="thumbnail"
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id="article-image-10"
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/49ac0506de6f/fcell-10-945586-g011.gif"
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alt="FIGURE 11" />
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<strong class="figure-label">
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<p> FIGURE 11 </p>
|
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</strong>
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|
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|
||
|
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<div class="figure-caption-contents"><p> Correlation analysis between <i> SLC22A17 </i> gene/isoforms… </p></div>
|
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|
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<strong class="figure-label">
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<p> FIGURE 11 </p>
|
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</strong>
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<div class="figure-caption-contents"><p> Correlation analysis between <i> SLC22A17 </i> gene/isoforms expression and relative CG probesets methylation levels in… </p></div>
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</div>
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<figcaption id="figure-caption-10" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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<strong class="figure-label">
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FIGURE 11
|
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</strong>
|
||
|
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|
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|
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<div class="figure-caption-contents">Correlation analysis between <i>SLC22A17</i> gene/isoforms expression and relative CG probesets methylation levels in each tumor type. <b>(A)</b> Volcano plot showing the correlation between CG probesets and gene/isoforms expression of <i>SLC22A17</i> (Pearson’s r ≥ 0.3 and ≤ −0.3, <i>p</i> ≤ 0.01). The top ten hits (five positive and five negative) based on correlation significance are labeled. Blue dots: negative correlation, red dots: positive correlation. <b>(B)</b> Percentage of tumor types, gene/isoforms and CG probesets showing Pearson’s r ≥ 0.3 and ≤ −0.3 (<i>p</i> ≤ 0.01), separately. No more than ten variables with the highest correlation values are indicated.</div>
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/101231b7da4d/fcell-10-945586-g012.jpg"
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role="button"
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data-image-width="617"
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data-image-height="735"
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data-image-alt="FIGURE 12"
|
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data-pmc-id="PMC9532607"
|
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data-figure-id="F12">
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<img class="figure-thumb" itemprop="thumbnail"
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id="article-image-11"
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||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/4fece4a2a550/fcell-10-945586-g012.gif"
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alt="FIGURE 12" />
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<strong class="figure-label">
|
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<p> FIGURE 12 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Correlation analysis between <i> MMP9 </i> isoforms… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
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||
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||
|
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|
||
|
||
|
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<strong class="figure-label">
|
||
<p> FIGURE 12 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Correlation analysis between <i> MMP9 </i> isoforms expression and relative CG probesets methylation levels in… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
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<figcaption id="figure-caption-11" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
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|
||
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|
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|
||
|
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|
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<strong class="figure-label">
|
||
FIGURE 12
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">Correlation analysis between <i>MMP9</i> isoforms expression and relative CG probesets methylation levels in each tumor type. <b>(A)</b> Volcano plot showing the correlation between CG probesets and isoforms expression of <i>MMP9</i> (Pearson’s r ≥ 0.3 and ≤ −0.3, <i>p</i> ≤ 0.01). The top ten hits (five positive and five negative) based on correlation significance are labeled. Blue dots: negative correlation, red dots: positive correlation. <b>(B)</b> Percentage of tumor types, gene/isoforms and CG probesets showing Pearson’s r ≥ 0.3 and ≤ −0.3 (<i>p</i> ≤ 0.01), separately. No more than ten variables with the highest correlation values are indicated.</div>
|
||
|
||
|
||
|
||
|
||
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|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-12"
|
||
role="button"
|
||
data-image-width="638"
|
||
data-image-height="572"
|
||
data-image-alt="FIGURE 13"
|
||
data-pmc-id="PMC9532607"
|
||
data-figure-id="F13">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-12"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/390a063962c6/fcell-10-945586-g013.gif"
|
||
alt="FIGURE 13" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="638">
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<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="572">
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|
||
|
||
|
||
|
||
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<strong class="figure-label">
|
||
<p> FIGURE 13 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Synergic effect of promoter hypomethylation… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 13 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Synergic effect of promoter hypomethylation and body hypermethylation in the upregulation of <i> SLC22A17… </i> </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-12" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 13
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">Synergic effect of promoter hypomethylation and body hypermethylation in the upregulation of <i>SLC22A17</i>. <b>(A)</b> Correlation analysis between gene expression (ENSG00000092096.14) and CG probesets methylation levels of <i>SLC22A17</i> was evaluated for each tumor type. Only CG probesets showing Pearson’s r ≥ 0.3 (magenta circles) and r ≤ −0.3 (green circles) <i>p</i> (≤0.05) are included. Magenta dots indicate the cg16420801 probeset while green dots represent the cg23464698 probeset. Green label indicates tumor types in which both CG probesets are significantly correlated. <b>(B)</b> Differential analysis (two-tailed unpaired <i>t</i>-test) of <i>SLC22A17</i> (ENSG00000092096.14) expression was performed stratifying the tumor samples in different four groups based on the methylation levels of cg16420801 and cg23464698 probesets with respect to the mean value calculated for each CG probeset in all tumor samples. FC and pValue are reported for each comparing group.</div>
|
||
|
||
|
||
|
||
|
||
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|
||
|
||
|
||
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||
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|
||
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|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/56c7961ff073/fcell-10-945586-g014.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-13"
|
||
role="button"
|
||
data-image-width="617"
|
||
data-image-height="762"
|
||
data-image-alt="FIGURE 14"
|
||
data-pmc-id="PMC9532607"
|
||
data-figure-id="F14">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-13"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/afb3a4064519/fcell-10-945586-g014.gif"
|
||
alt="FIGURE 14" />
|
||
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|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="617">
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<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="762">
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|
||
|
||
|
||
|
||
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||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 14 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> OS analysis according to methylation… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
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|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 14 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> OS analysis according to methylation levels of CG probesets relative to <i> LCN2 </i> ,… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-13" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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||
|
||
|
||
|
||
|
||
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<strong class="figure-label">
|
||
FIGURE 14
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">OS analysis according to methylation levels of CG probesets relative to <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> in all tumor types. The CG probesets statistically associated (<i>p</i> ≤ 0.05) with OS are represented in the heatmap.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
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||
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href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/78cec7dcce2e/fcell-10-945586-g015.jpg"
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data-image-width="645"
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data-image-alt="FIGURE 15"
|
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data-pmc-id="PMC9532607"
|
||
data-figure-id="F15">
|
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<img class="figure-thumb" itemprop="thumbnail"
|
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||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/9532607/122f2f4fefcf/fcell-10-945586-g015.gif"
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<p> FIGURE 15 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> PFI analysis according to methylation… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
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|
||
|
||
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|
||
|
||
|
||
|
||
|
||
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||
|
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<strong class="figure-label">
|
||
<p> FIGURE 15 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> PFI analysis according to methylation levels of CG probesets relative to <i> LCN2 </i> ,… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-14" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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||
|
||
|
||
|
||
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<strong class="figure-label">
|
||
FIGURE 15
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">PFI analysis according to methylation levels of CG probesets relative to <i>LCN2</i>, <i>SLC22A17</i>, and <i>MMP9</i> in all tumor types. The CG probesets statistically associated (<i>p</i> ≤ 0.05) with PFI are represented in the heatmap.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
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||
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Abba M., Patil N., Allgayer H. (2014). MicroRNAs in the regulation of MMPs and metastasis. Cancers (Basel) 6, 625–645. 10.3390/cancers6020625
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