Single-cell atlas of tumor clonal evolution in liver cancer
Single-cell atlas of tumor clonal evolution in liver cancer
SUMMARY Tumor evolution is a key feature of tumorigenesis and plays a pivotal role in driving intratumor heterogeneity, treatment failure and patients’ prognosis. Here we performed single-cell transcriptome profiling of 46 primary liver cancers from 37 patients enrolled for interventional studies. We surveyed the landscape of ~57,000 malignant and non-malignant cells and determined tumor cell clonality by developing a machine learning-based consensus clustering method. We found evidence of tumor cell branching evolution using hierarchical clustering, RNA velocity as well as reverse graph embedding methods. Interestingly, an increasing tumor cell clonality was tightly linked to patients’ prognosis, accompanied by a polarized immune cell landscape. We identified osteopontin as a key player for tumor cell evolution and microenvironmental reprogramming. Our study offers insight into the collective behavior of tumor cell communities in liver cancer as well as potential drivers for tumor evolution in response to therapy.
Wang Limin、Ma Lichun、Tran Bao、Dominguez Dana、Forgues Marshonna、Hernandez Maria O.、Davis Jeremy L.、Wood Bradford J.、Heinrich Sophia、Wang Xin Wei、Hernandez Jonathan M.、Kelly Michael、Kleiner David E.、Candia Juli¨￠n、Chang Ching-Wen、Greten Tim F.、Zhao Yongmei
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteFrederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteFrederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.Surgical Oncology Program, Center for Cancer Research, National Cancer InstituteLiver Cancer Program, Center for Cancer Research, National Cancer Institute||NIH Center for Interventional OncologyLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute||Liver Cancer Program, Center for Cancer Research, National Cancer InstituteSurgical Oncology Program, Center for Cancer Research, National Cancer InstituteFrederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.Laboratory of Pathology, Center for Cancer Research, National Cancer Institute||Liver Cancer Program, Center for Cancer Research, National Cancer InstituteLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteLiver Cancer Program, Center for Cancer Research, National Cancer Institute||Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer InstituteFrederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.
肿瘤学生物科学研究方法、生物科学研究技术细胞生物学
ClonalityTumor evolutionLiver cancerHepatocellular carcinomaCholangiocarcinomaSingle cellTumor heterogeneityTumor microenvironmentsT cellsOsteopontin
Wang Limin,Ma Lichun,Tran Bao,Dominguez Dana,Forgues Marshonna,Hernandez Maria O.,Davis Jeremy L.,Wood Bradford J.,Heinrich Sophia,Wang Xin Wei,Hernandez Jonathan M.,Kelly Michael,Kleiner David E.,Candia Juli¨￠n,Chang Ching-Wen,Greten Tim F.,Zhao Yongmei.Single-cell atlas of tumor clonal evolution in liver cancer[EB/OL].(2025-03-28)[2025-05-02].https://www.biorxiv.org/content/10.1101/2020.08.18.254748.点此复制
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