{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:09:22Z","timestamp":1790975362575,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100678"],"award-info":[{"award-number":["82100678"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["23ZR1440800"],"award-info":[{"award-number":["23ZR1440800"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"publisher","award":["20214Y0223"],"award-info":[{"award-number":["20214Y0223"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Thyroid cancer is one of the most common endocrine tumors worldwide, especially among women and the metastatic mechanism of papillary thyroid carcinoma remains poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thyroid cancer tissue samples were obtained for single\u2010cell RNA\u2010sequencing and spatial transcriptomics, aiming to intratumoral and antimetastatic heterogeneity of advanced PTC. The functions of <jats:italic>APOE<\/jats:italic> in PTC cell proliferation and invasion were confirmed through in vivo and in vitro assays. Pseudotime analysis and CellChat were performed to explore the the molecular mechanisms of the <jats:italic>APOE<\/jats:italic> in PTC progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a subpopulation of tumor cells with lower expression levels of <jats:italic>APOE<\/jats:italic>, associated with advanced stages of PTC and cervical metastasis. <jats:italic>APOE<\/jats:italic> overexpression significantly reduced tumor cell proliferation and invasion, both in vitro and in vivo, by activating the <jats:italic>ABCA1\u2010LXR<\/jats:italic> axis. <jats:italic>APOE<jats:sup>\u2212<\/jats:sup><\/jats:italic> tumor cells may promote tumor growth by interacting with dendritic cells and CD4<jats:sup>+<\/jats:sup> T cells via <jats:italic>CD99<\/jats:italic>\u2010 rather than CD6\u2010regulated signaling. We established a machine learning\u2010based scRNA\u2010seq data, 13\u2010gene signature predictive of lymph node metastasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified a distinct <jats:italic>APOE<jats:sup>\u2212<\/jats:sup><\/jats:italic> tumor cell population associated with cervical metastasis and poor prognosis. Our results and models have potential clinical, prognostic, and therapeutic implications for advanced PTC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>A subpopulation of tumor cells with lower expression levels of <jats:italic>APOE<\/jats:italic> was strongly associated with more advanced stages and metastasis of PTC.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:italic>APOE<\/jats:italic>\u2010negative (<jats:italic>APOE<\/jats:italic><jats:sup>\u2212<\/jats:sup>) cellsoverall exhibited weaker interactions with immune cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A machine\u2010learning bioinformatics model based on scRNA\u2010seq data of in\u2010situ thyroid cancer tissue was established to predict lymph node metastasis.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.70172","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T03:40:31Z","timestamp":1736912431000},"source":"Crossref","is-referenced-by-count":17,"title":["Single\u2010cell RNA\u2010sequencing and spatial transcriptomic analysis reveal a distinct population of <i>APOE<\/i><sup>\u2212<\/sup> cells yielding pathological lymph node metastasis in papillary thyroid cancer"],"prefix":"10.1002","volume":"15","author":[{"given":"Guohui","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of General Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongli","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of General Surgery Ruijin Hospital Luwan Branch Shanghai Jiao Tong University School of Medicine  Shanghai 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