Identification of hepatocellular carcinoma subtypes based on PcG-related genes and biological relevance with cancer cells

Clinical Epigenetics

Research

Yujie Deng¹  Yunong Fu²  Kaibo Yang²  Kun Yang²  Hai Wang²  Qing Yao²  Kunjin Wu²  Fengping Zhang²  Kai Qu²  Xiaohua Ma²  Qinglin Li²  Chang Liu³  Jingyao Zhang⁴ 

[1] Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China;Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, 710061, Xi’an, Shaanxi, China;Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, 710061, Xi’an, Shaanxi, China;Department of Surgical Intensive Care Units, The First Affiliated Hospital of Xi’an Jiaotong University, 710061, Xi’an, Shaanxi, China;Department of Surgical Intensive Care Units, The First Affiliated Hospital of Xi’an Jiaotong University, 710061, Xi’an, Shaanxi, China;

关键词: Hepatocellular carcinoma;    Polycomb group proteins;    Cancer subtype;    Chemotherapy sensitivity;    Cell metabolism;   

DOI  :  10.1186/s13148-022-01393-6

 received in 2022-05-12, accepted in 2022-11-30,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundHepatocellular carcinoma (HCC) is an extensive heterogeneous disease where epigenetic factors contribute to its pathogenesis. Polycomb group (PcG) proteins are a group of subunits constituting various macro-molecular machines to regulate the epigenetic landscape, which contributes to cancer phenotype and has the potential to develop a molecular classification of HCC.ResultsHere, based on multi-omics data analysis of DNA methylation, mRNA expression, and copy number of PcG-related genes, we established an epigenetic classification system of HCC, which divides the HCC patients into two subgroups with significantly different outcomes. Comparing these two epigenetic subgroups, we identified different metabolic features, which were related to epigenetic regulation of polycomb-repressive complex 1/2 (PRC1/2). Furthermore, we experimentally proved that inhibition of PcG complexes enhanced the lipid metabolism and reduced the capacity of HCC cells against glucose shortage. In addition, we validated the low chemotherapy sensitivity of HCC in Group A and found inhibition of PRC1/2 promoted HCC cells’ sensitivity to oxaliplatin in vitro and in vivo. Finally, we found that aberrant upregulation of CBX2 in Group A and upregulation of CBX2 were associated with poor prognosis in HCC patients. Furthermore, we found that manipulation of CBX2 affected the levels of H3K27me3 and H2AK119ub.ContributionsOur study provided a novel molecular classification system based on PcG-related genes data and experimentally validated the biological features of HCC in two subgroups. Our founding supported the polycomb complex targeting strategy to inhibit HCC progression where CBX2 could be a feasible therapeutic target.

【 授权许可】

CC BY   
© The Author(s) 2022

【 图 表 】

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