Transferrin receptor-based circulating tumor cell enrichment provides a snapshot of the molecular landscape of solid tumors and correlates with clinical outcomes

<!DOCTYPE html> <html lang="en" > <head > <meta charset="UTF-8" /> <meta http-equiv="X-UA-Compatible" content="IE=edge" /> <meta name="HandheldFriendly" content="True" /> <meta name="MobileOptimized" content="320" /> <meta name="viewport" content="width=device-width, initial-scale=1.0" /> <link rel="stylesheet" href="/static/assets/style-70b9163a.css" /> <script type="module" crossorigin="" src="/static/assets/base_style-ec2bc71e.js"></script> <link rel="stylesheet" href="/static/assets/style-ef962842.css" /> <link rel="stylesheet" href="/static/assets/style-3ade8b5c.css" /> <script type="module" crossorigin="" src="/static/assets/article_style-d757a0dd.js"></script> <style> @media screen and (min-width: 64em) { div.pmc-wm { background: repeat-y; background-image: url("data:image/svg+xml,%3Csvg xmlns='http://www.w3.org/2000/svg' width='20' height='350' xmlns:xlink='http://www.w3.org/1999/xlink'%3E%3Cdefs%3E%3Cfilter x='-.02' y='0' width='1.05' height='1' id='c'%3E%3CfeFlood flood-color='%23FFF'/%3E%3CfeComposite in='SourceGraphic'/%3E%3C/filter%3E%3Ctext id='b' font-family='Helvetica' font-size='11pt' style='opacity:1;fill:%23005ea2;stroke:none;text-anchor:middle' x='175' y='14'%3EPreprint%3C/text%3E%3Cpath id='a' style='fill:%23005ea2' d='M0 8h350v3H0z'/%3E%3C/defs%3E%3Cuse xlink:href='%23a' transform='rotate(90 10 10)'/%3E%3Cuse xlink:href='%23b' transform='rotate(90 10 10)' filter='url(%23c)'/%3E%3C/svg%3E"); padding-left: 3rem; } } </style> <link rel="apple-touch-icon" sizes="180x180" href="/static/img/favicons/apple-touch-icon.png" /> <link rel="icon" type="image/png" sizes="48x48" href="/static/img/favicons/favicon-48x48.png" /> <link rel="icon" type="image/png" sizes="32x32" href="/static/img/favicons/favicon-32x32.png" /> <link rel="icon" type="image/png" sizes="16x16" href="/static/img/favicons/favicon-16x16.png" /> <link rel="manifest" href="/static/img/favicons/site.webmanifest" /> <link rel="mask-icon" href="/static/img/favicons/safari-pinned-tab.svg" color="#0071bc" /> <meta name="msapplication-config" content="/static/img/favicons/browserconfig.xml" /> <meta name="theme-color" content="#ffffff" /> <title> Transferrin receptor-based circulating tumor cell enrichment provides a snapshot of the molecular landscape of solid tumors and correlates with clinical outcomes - PMC </title>  <meta name="ncbi_app" content="cloudpmc-viewer" /> <meta name="ncbi_db" content="pmc" /> <meta name="ncbi_phid" content="E5FD0244746DC003060244002C4587B5.m_1" />  <meta name="ncbi_pdid" content="article" /> <link rel="preconnect" href="https://www.google-analytics.com" /> <link rel="dns-prefetch" href="https://cdn.ncbi.nlm.nih.gov" /> <link rel="preconnect" href="https://code.jquery.com" /> <meta name="ncbi_domain" content="medrxiv"> <meta name="ncbi_type" content="fulltext"> <meta name="ncbi_pcid" content="preprint"> <link rel="canonical" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC11213041/"> <meta name="robots" content="INDEX,NOFOLLOW,NOARCHIVE"> <meta name="citation_journal_title" content="medRxiv"> <meta name="citation_title" content="Transferrin receptor-based circulating tumor cell enrichment provides a snapshot of the molecular landscape of solid tumors and correlates with clinical outcomes"> <meta name="citation_author" content="Giuseppe Galletti"> <meta name="citation_author" content="Ahmed Halima"> <meta name="citation_author" content="Ada Gjyrezi"> <meta name="citation_author" content="Jiaren Zhang"> <meta name="citation_author" content="Bob Zimmerman"> <meta name="citation_author" content="Daniel Worroll"> <meta name="citation_author" content="Galatea Kallergi"> <meta name="citation_author" content="Rohan Barreja"> <meta name="citation_author" content="Allyson Ocean"> <meta name="citation_author" content="Ashish Saxena"> <meta name="citation_author" content="Timothy E McGraw"> <meta name="citation_author" content="David M Nanus"> <meta name="citation_author" content="Olivier Elemento"> <meta name="citation_author" content="Nasser K Altorki"> <meta name="citation_author" content="Scott T Tagawa"> <meta name="citation_author" content="Paraskevi Giannakakou"> <meta name="citation_publication_date" content="2024 Jun 17"> <meta name="citation_firstpage" content="2024.06.16.24309003"> <meta name="citation_doi" content="10.1101/2024.06.16.24309003"> <meta name="citation_pmid" content="38947080"> <meta name="citation_abstract_html_url" content="https://pmc.ncbi.nlm.nih.gov/articles/PMC11213041/"> <meta name="citation_fulltext_html_url" content="https://pmc.ncbi.nlm.nih.gov/articles/PMC11213041/"> <meta name="description" content="Circulating tumor cells (CTCs) captured from the bloodstream of patients with solid tumors have the potential to accelerate precision oncology by providing insight into tumor biology, disease progression and response to treatment. 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class="front-matter"><div class="ameta p font-secondary font-xs"> <hgroup><h1> Transferrin receptor-based circulating tumor cell enrichment provides a snapshot of the molecular landscape of solid tumors and correlates with clinical outcomes </h1></hgroup><div class="cg p"> <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Galletti%20G%22%5BAuthor%5D" class="usa-link" aria-describedby="id1"><span class="name western">Giuseppe Galletti</span></a><div hidden="hidden" id="id1"> <h3><span class="name western">Giuseppe Galletti</span></h3> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Galletti%20G%22%5BAuthor%5D" class="usa-link"><span class="name western">Giuseppe Galletti</span></a> </div> </div>, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Halima%20A%22%5BAuthor%5D" class="usa-link" aria-describedby="id2"><span class="name western">Ahmed Halima</span></a><div hidden="hidden" id="id2"> <h3><span class="name western">Ahmed Halima</span></h3> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Halima%20A%22%5BAuthor%5D" class="usa-link"><span class="name western">Ahmed Halima</span></a> </div> </div>, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Gjyrezi%20A%22%5BAuthor%5D" class="usa-link" aria-describedby="id3"><span class="name western">Ada Gjyrezi</span></a><div hidden="hidden" id="id3"> <h3><span class="name western">Ada Gjyrezi</span></h3> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Gjyrezi%20A%22%5BAuthor%5D" class="usa-link"><span class="name western">Ada Gjyrezi</span></a> </div> </div>, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Zhang%20J%22%5BAuthor%5D" class="usa-link" aria-describedby="id4"><span class="name western">Jiaren Zhang</span></a><div hidden="hidden" id="id4"> <h3><span class="name western">Jiaren Zhang</span></h3> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Zhang%20J%22%5BAuthor%5D" class="usa-link"><span class="name western">Jiaren Zhang</span></a> </div> </div>, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Zimmerman%20B%22%5BAuthor%5D" class="usa-link" aria-describedby="id5"><span class="name western">Bob Zimmerman</span></a><div hidden="hidden" id="id5"> <h3><span class="name western">Bob Zimmerman</span></h3> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Zimmerman%20B%22%5BAuthor%5D" class="usa-link"><span class="name western">Bob Zimmerman</span></a> </div> </div>, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Worroll%20D%22%5BAuthor%5D" class="usa-link" aria-describedby="id6"><span class="name western">Daniel Worroll</span></a><div hidden="hidden" id="id6"> <h3><span class="name western">Daniel Worroll</span></h3> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Worroll%20D%22%5BAuthor%5D" class="usa-link"><span class="name western">Daniel Worroll</span></a> </div> </div>, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Kallergi%20G%22%5BAuthor%5D" class="usa-link" aria-describedby="id7"><span class="name western">Galatea Kallergi</span></a><div hidden="hidden" id="id7"> <h3><span class="name western">Galatea Kallergi</span></h3> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Kallergi%20G%22%5BAuthor%5D" class="usa-link"><span class="name western">Galatea Kallergi</span></a> </div> </div>, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Barreja%20R%22%5BAuthor%5D" class="usa-link" aria-describedby="id8"><span class="name western">Rohan Barreja</span></a><div hidden="hidden" id="id8"> <h3><span class="name western">Rohan Barreja</span></h3> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Barreja%20R%22%5BAuthor%5D" class="usa-link"><span class="name western">Rohan Barreja</span></a> </div> </div>, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Ocean%20A%22%5BAuthor%5D" class="usa-link" aria-describedby="id9"><span class="name western">Allyson Ocean</span></a><div hidden="hidden" id="id9"> <h3><span class="name western">Allyson Ocean</span></h3> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Ocean%20A%22%5BAuthor%5D" class="usa-link"><span class="name western">Allyson Ocean</span></a> </div> </div>, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Saxena%20A%22%5BAuthor%5D" class="usa-link" aria-describedby="id10"><span class="name western">Ashish Saxena</span></a><div hidden="hidden" id="id10"> <h3><span class="name western">Ashish Saxena</span></h3> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Saxena%20A%22%5BAuthor%5D" class="usa-link"><span class="name western">Ashish Saxena</span></a> </div> </div>, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22McGraw%20TE%22%5BAuthor%5D" class="usa-link" aria-describedby="id11"><span class="name western">Timothy E McGraw</span></a><div hidden="hidden" id="id11"> <h3><span class="name western">Timothy E McGraw</span></h3> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22McGraw%20TE%22%5BAuthor%5D" class="usa-link"><span class="name western">Timothy E McGraw</span></a> </div> </div>, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Nanus%20DM%22%5BAuthor%5D" class="usa-link" aria-describedby="id12"><span class="name western">David M Nanus</span></a><div hidden="hidden" id="id12"> <h3><span class="name western">David M Nanus</span></h3> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Nanus%20DM%22%5BAuthor%5D" class="usa-link"><span class="name western">David M Nanus</span></a> </div> </div>, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Elemento%20O%22%5BAuthor%5D" class="usa-link" aria-describedby="id13"><span class="name western">Olivier Elemento</span></a><div hidden="hidden" id="id13"> <h3><span class="name western">Olivier Elemento</span></h3> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Elemento%20O%22%5BAuthor%5D" class="usa-link"><span class="name western">Olivier Elemento</span></a> </div> </div>, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Altorki%20NK%22%5BAuthor%5D" class="usa-link" aria-describedby="id14"><span class="name western">Nasser K Altorki</span></a><div hidden="hidden" id="id14"> <h3><span class="name western">Nasser K Altorki</span></h3> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Altorki%20NK%22%5BAuthor%5D" class="usa-link"><span class="name western">Nasser K Altorki</span></a> </div> </div>, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Tagawa%20ST%22%5BAuthor%5D" class="usa-link" aria-describedby="id15"><span class="name western">Scott T Tagawa</span></a><div hidden="hidden" id="id15"> <h3><span class="name western">Scott T Tagawa</span></h3> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Tagawa%20ST%22%5BAuthor%5D" class="usa-link"><span class="name western">Scott T Tagawa</span></a> </div> </div>, <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Giannakakou%20P%22%5BAuthor%5D" class="usa-link" aria-describedby="id16"><span class="name western">Paraskevi Giannakakou</span></a><div hidden="hidden" id="id16"> <h3><span class="name western">Paraskevi Giannakakou</span></h3> <div class="p">Find articles by <a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Giannakakou%20P%22%5BAuthor%5D" class="usa-link"><span class="name western">Paraskevi Giannakakou</span></a> </div> </div> </div> <ul class="d-buttons inline-list"><li><button class="d-button" aria-controls="clp_a" aria-expanded="false">Copyright and License information</button></li></ul> <div class="d-panels font-secondary-light"><div id="clp_a" class="d-panel p" style="display: none"><div class="p"><a href="/about/copyright/" class="usa-link">PMC Copyright notice</a></div></div></div> <div>PMCID: PMC11213041 PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/38947080/" class="usa-link">38947080</a> </div> <div class="ra xbox p" role="complementary" aria-label="Related or updated information about this article"><div>The complete version history of this preprint is available at <a href="https://doi.org/10.1101/2024.06.16.24309003" class="usa-link usa-link--external" data-ga-action="click_feat_suppl" target="_blank" rel="noopener noreferrer">medRxiv</a>.</div></div> </div></section></section><section aria-label="Article content"><section class="body main-article-body"><section class="abstract" id="abstract1"><h2>Abstract</h2> <p> Circulating tumor cells (CTCs) captured from the bloodstream of patients with solid tumors have the potential to accelerate precision oncology by providing insight into tumor biology, disease progression and response to treatment. However, their potential is hampered by the lack of standardized CTC enrichment platforms across tumor types. EpCAM-based CTC enrichment, the most commonly used platform, is limited by EpCAM downregulation during metastasis and the low EpCAM expression in certain tumor types, including the highly prevalent and lethal NSCLC. In this study we demonstrate that Transferrin Receptor (TfR) is a selective, efficient biomarker for CTC identification and capture in patients with prostate, pancreatic and NSCLC. TfR identifies significantly higher CTC counts than EpCAM, and TfR <sup>+</sup> -CTC enumeration correlates with disease progression in metastatic prostate and pancreatic cancers, and overall survival and osimetrinib-resistance in non-small cell lung cancer (NSCLC). Profiling of TfR <sup>+</sup> -CTCs provides a snapshot of the molecular landscape of each respective tumor type and identifies potential mechanisms underlying treatment response to EGFR TKi and immune checkpoint inhibitors in NSCLC. </p> <section id="sec1"><h3 class="pmc_sec_title">One sentence summary</h3> <p>Transferrin Receptor identifies circulating tumor cells in solid tumors</p></section></section><section id="sec2"><h2 class="pmc_sec_title">Full Text Availability</h2> <p>The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. 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Transferrin receptor-based circulating tumor cell enrichment provides a snapshot of the molecular landscape of solid tumors and correlates with clinical outcomes - PMC