Single‐cell RNA‐sequencing and spatial transcriptomic analysis reveal a distinct population of APOE− cells yielding pathological lymph node metastasis in papillary thyroid cancer
Abstract 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 transc...
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2025-01-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | https://doi.org/10.1002/ctm2.70172 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Guohui Xiao |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-a3d2918b36f8477f98f94d710434ac9a |
| institution | Kabale University |
| issn | 2001-1326 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj-art-a3d2918b36f8477f98f94d710434ac9a2025-01-25T04:00:38ZengWileyClinical and Translational Medicine2001-13262025-01-01151n/an/a10.1002/ctm2.70172Single‐cell RNA‐sequencing and spatial transcriptomic analysis reveal a distinct population of APOE− cells yielding pathological lymph node metastasis in papillary thyroid cancerGuohui Xiao0Rongli Xie1Jianhua Gu2Yishu Huang3Min Ding4Dongjie Shen5Jiqi Yan6Jianming Yuan7Qiong Yang8Wen He9Siyu Xiao10Haizhen Chen11Dan Xu12Jian Wu13Jian Fei14Department of General Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of General Surgery Ruijin Hospital Luwan Branch Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Thyroid and Breast Surgery Punan Branch of Renji Hospital Shanghai Jiaotong University School of Medicine Shanghai ChinaDepartment of General Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of General Surgery Ruijin Hospital Luwan Branch Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of General Surgery Ruijin Hospital Luwan Branch Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of General Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of General Surgery Ruijin Hospital Luwan Branch Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of General Surgery Shanghai Changhang Hospital Shanghai ChinaDepartment of General Surgery Shanghai International Medical Center Shanghai ChinaDepartment of General Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of General Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Emergency Medicine Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaDepartment of Pathology Punan Branch of Renji Hospital Jiaotong University School of Medicine Shanghai ChinaDepartment of General Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai ChinaAbstract 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.https://doi.org/10.1002/ctm2.70172APOE‐ABCA1‐LXR axislymph node metastasispapillary thyroid carcinomasingle‐cell RNA‐sequencing |
| spellingShingle | 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 Single‐cell RNA‐sequencing and spatial transcriptomic analysis reveal a distinct population of APOE− cells yielding pathological lymph node metastasis in papillary thyroid cancer Clinical and Translational Medicine APOE‐ABCA1‐LXR axis lymph node metastasis papillary thyroid carcinoma single‐cell RNA‐sequencing |
| 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 |
| title_full | Single‐cell RNA‐sequencing and spatial transcriptomic analysis reveal a distinct population of APOE− cells yielding pathological lymph node metastasis in papillary thyroid cancer |
| title_fullStr | Single‐cell RNA‐sequencing and spatial transcriptomic analysis reveal a distinct population of APOE− cells yielding pathological lymph node metastasis in papillary thyroid cancer |
| title_full_unstemmed | Single‐cell RNA‐sequencing and spatial transcriptomic analysis reveal a distinct population of APOE− cells yielding pathological lymph node metastasis in papillary thyroid cancer |
| title_short | Single‐cell RNA‐sequencing and spatial transcriptomic analysis reveal a distinct population of APOE− cells yielding pathological lymph node metastasis in papillary thyroid cancer |
| title_sort | single cell rna sequencing and spatial transcriptomic analysis reveal a distinct population of apoe cells yielding pathological lymph node metastasis in papillary thyroid cancer |
| topic | APOE‐ABCA1‐LXR axis lymph node metastasis papillary thyroid carcinoma single‐cell RNA‐sequencing |
| url | https://doi.org/10.1002/ctm2.70172 |
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