IDH Mutation Subgroup Status Associates with Intratumor Heterogeneity and the Tumor Microenvironment in Intrahepatic Cholangiocarcinoma.

Autor: Xiang X; Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Beijing, 100044, China., Liu Z; Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, 100871, China.; Beijing Advanced Innovation Center for Genomics (ICG), Peking University, Beijing, 100871, China., Zhang C; Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, 100871, China.; Beijing Advanced Innovation Center for Genomics (ICG), Peking University, Beijing, 100871, China., Li Z; Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Beijing, 100044, China., Gao J; Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Beijing, 100044, China., Zhang C; Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Beijing, 100044, China., Cao Q; Translational Cancer Research Center, Peking University First Hospital, Beijing, 100034, China., Cheng J; Translational Cancer Research Center, Peking University First Hospital, Beijing, 100034, China., Liu H; Translational Cancer Research Center, Peking University First Hospital, Beijing, 100034, China., Chen D; Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Beijing, 100044, China., Cheng Q; Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Beijing, 100044, China., Zhang N; Translational Cancer Research Center, Peking University First Hospital, Beijing, 100034, China., Xue R; Translational Cancer Research Center, Peking University First Hospital, Beijing, 100034, China., Bai F; Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, 100871, China.; Beijing Advanced Innovation Center for Genomics (ICG), Peking University, Beijing, 100871, China., Zhu J; Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing Key Surgical Basic Research Laboratory of Liver Cirrhosis and Liver Cancer, Beijing, 100044, China.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2021 Sep; Vol. 8 (17), pp. e2101230. Date of Electronic Publication: 2021 Jul 11.
DOI: 10.1002/advs.202101230
Abstrakt: Intrahepatic cholangiocarcinoma (ICC) is highly heterogeneous. Here, the authors perform exome sequencing and bulk RNA sequencing on 73 tumor regions from 14 ICC patients to portray the multi-faceted intratumor heterogeneity (ITH) landscape of ICC. The authors show that ITH is highly concordant across genomic, transcriptomic, and immune levels. Comparison of these data to 8 published datasets reveals significantly higher degrees of ITH in ICC than hepatocellular carcinoma. Remarkably, the authors find that high-ITH tumors highly overlap with the IDH (isocitrate dehydrogenase)-mutant subgroup (IDH-SG), comprising of IDH-mutated tumors and IDH-like tumors, that is, those IDH-wildtype tumors that exhibit similar molecular profiles to the IDH-mutated ones. Furthermore, IDH-SG exhibits less T cell infiltration and lower T cell cytotoxicity, indicating a colder tumor microenvironment (TME). The higher ITH and colder TME of IDH-SG are successfully validated by single-cell RNA sequencing on 17 503 cells from 4 patients. Collectively, the study shows that IDH mutant subgroup status, rather than IDH mutation alone, is associated with ITH and the TME of ICC tumors. The results highlight that IDH-like patients may also benefit from IDH targeted therapies and provide important implications for the diagnosis and treatment of ICC.
(© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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