{"title":"单细胞rna测序和空间转录组学分析显示，APOE-细胞在甲状腺乳头状癌中产生病理性淋巴结转移。","authors":"Guohui Xiao, Rongli Xie, Jianhua Gu, Yishu Huang, Min Ding, Dongjie Shen, Jiqi Yan, Jianming Yuan, Qiong Yang, Wen He, Siyu Xiao, Haizhen Chen, Dan Xu, Jian Wu, Jian Fei","doi":"10.1002/ctm2.70172","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Thyroid cancer tissue samples were obtained for single-cell RNA-sequencing and spatial transcriptomics, aiming to intratumoral and antimetastatic heterogeneity of advanced PTC. The functions of <i>APOE</i> 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 <i>APOE</i> in PTC progression.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>We identified a subpopulation of tumor cells with lower expression levels of <i>APOE</i>, associated with advanced stages of PTC and cervical metastasis. <i>APOE</i> overexpression significantly reduced tumor cell proliferation and invasion, both in vitro and in vivo, by activating the <i>ABCA1-LXR</i> axis. <i>APOE<sup>−</sup></i> tumor cells may promote tumor growth by interacting with dendritic cells and CD4<sup>+</sup> T cells via <i>CD99</i>- rather than CD6-regulated signaling. We established a machine learning-based scRNA-seq data, 13-gene signature predictive of lymph node metastasis.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>We identified a distinct <i>APOE<sup>−</sup></i> tumor cell population associated with cervical metastasis and poor prognosis. Our results and models have potential clinical, prognostic, and therapeutic implications for advanced PTC.</p>\n </section>\n \n <section>\n \n <h3> Key points</h3>\n \n <div>\n <ul>\n \n <li>A subpopulation of tumor cells with lower expression levels of <i>APOE</i> was strongly associated with more advanced stages and metastasis of PTC.</li>\n \n <li><i>APOE</i>-negative (<i>APOE</i><sup>−</sup>) cellsoverall exhibited weaker interactions with immune cells.</li>\n \n <li>A machine-learning bioinformatics model based on scRNA-seq data of in-situ thyroid cancer tissue was established to predict lymph node metastasis.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 1","pages":""},"PeriodicalIF":7.9000,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733439/pdf/","citationCount":"0","resultStr":"{\"title\":\"Single-cell RNA-sequencing and spatial transcriptomic analysis reveal a distinct population of APOE− cells yielding pathological lymph node metastasis in papillary thyroid cancer\",\"authors\":\"Guohui Xiao, Rongli Xie, Jianhua Gu, Yishu Huang, Min Ding, Dongjie Shen, Jiqi Yan, Jianming Yuan, Qiong Yang, Wen He, Siyu Xiao, Haizhen Chen, Dan Xu, Jian Wu, Jian Fei\",\"doi\":\"10.1002/ctm2.70172\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Thyroid cancer tissue samples were obtained for single-cell RNA-sequencing and spatial transcriptomics, aiming to intratumoral and antimetastatic heterogeneity of advanced PTC. The functions of <i>APOE</i> 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 <i>APOE</i> in PTC progression.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>We identified a subpopulation of tumor cells with lower expression levels of <i>APOE</i>, associated with advanced stages of PTC and cervical metastasis. <i>APOE</i> overexpression significantly reduced tumor cell proliferation and invasion, both in vitro and in vivo, by activating the <i>ABCA1-LXR</i> axis. <i>APOE<sup>−</sup></i> tumor cells may promote tumor growth by interacting with dendritic cells and CD4<sup>+</sup> T cells via <i>CD99</i>- rather than CD6-regulated signaling. We established a machine learning-based scRNA-seq data, 13-gene signature predictive of lymph node metastasis.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>We identified a distinct <i>APOE<sup>−</sup></i> tumor cell population associated with cervical metastasis and poor prognosis. Our results and models have potential clinical, prognostic, and therapeutic implications for advanced PTC.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Key points</h3>\\n \\n <div>\\n <ul>\\n \\n <li>A subpopulation of tumor cells with lower expression levels of <i>APOE</i> was strongly associated with more advanced stages and metastasis of PTC.</li>\\n \\n <li><i>APOE</i>-negative (<i>APOE</i><sup>−</sup>) cellsoverall exhibited weaker interactions with immune cells.</li>\\n \\n <li>A machine-learning bioinformatics model based on scRNA-seq data of in-situ thyroid cancer tissue was established to predict lymph node metastasis.</li>\\n </ul>\\n </div>\\n </section>\\n </div>\",\"PeriodicalId\":10189,\"journal\":{\"name\":\"Clinical and Translational Medicine\",\"volume\":\"15 1\",\"pages\":\"\"},\"PeriodicalIF\":7.9000,\"publicationDate\":\"2025-01-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733439/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Translational Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70172\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70172","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Single-cell RNA-sequencing and spatial transcriptomic analysis reveal a distinct population of APOE− cells yielding pathological lymph node metastasis in papillary thyroid cancer
Background
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.
Methods
Thyroid cancer tissue samples were obtained for single-cell RNA-sequencing and spatial transcriptomics, aiming to intratumoral and antimetastatic heterogeneity of advanced PTC. The functions of APOE 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 APOE in PTC progression.
Results
We identified a subpopulation of tumor cells with lower expression levels of APOE, associated with advanced stages of PTC and cervical metastasis. APOE overexpression significantly reduced tumor cell proliferation and invasion, both in vitro and in vivo, by activating the ABCA1-LXR axis. APOE− tumor cells may promote tumor growth by interacting with dendritic cells and CD4+ T cells via CD99- rather than CD6-regulated signaling. We established a machine learning-based scRNA-seq data, 13-gene signature predictive of lymph node metastasis.
Conclusions
We identified a distinct APOE− tumor cell population associated with cervical metastasis and poor prognosis. Our results and models have potential clinical, prognostic, and therapeutic implications for advanced PTC.
Key points
A subpopulation of tumor cells with lower expression levels of APOE was strongly associated with more advanced stages and metastasis of PTC.
APOE-negative (APOE−) cellsoverall exhibited weaker interactions with immune cells.
A machine-learning bioinformatics model based on scRNA-seq data of in-situ thyroid cancer tissue was established to predict lymph node metastasis.
期刊介绍：
Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
