Whole genome and RNA sequencing analyses for 254 Taiwanese hepatocellular carcinomas

Biomarker Research

Research

Ju-Chen Yen¹  Ya-Ting Lee¹  Chin-Chun Chung¹  Hong-Da Chen²  Ming-Hon Hsu²  Yu-Pao Chou²  Siang-Jyun Tu²  Jan-Gowth Chang³  Ya-Sian Chang³  Long-Bin Jeng⁴ 

[1] Center for Precision Medicine, China Medical University Hospital, 2 Yuh-Der Road, 404, Taichung, Taiwan;Epigenome Research Center, China Medical University Hospital, 2 Yuh-Der Road, 404, Taichung, Taiwan;Center for Precision Medicine, China Medical University Hospital, 2 Yuh-Der Road, 404, Taichung, Taiwan;Epigenome Research Center, China Medical University Hospital, 2 Yuh-Der Road, 404, Taichung, Taiwan;Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan;Center for Precision Medicine, China Medical University Hospital, 2 Yuh-Der Road, 404, Taichung, Taiwan;Epigenome Research Center, China Medical University Hospital, 2 Yuh-Der Road, 404, Taichung, Taiwan;Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan;School of Medicine, China Medical University, Taichung, Taiwan;Organ Transplantation Center, China Medical University Hospital, 2 Yuh-Der Road, 404, Taichung, Taiwan;

关键词: Whole genome sequencing;    RNA sequencing;    Taiwanese HCC;    Alternative splicing;    Immune checkpoint gene;    Tumor microenvironment;   

DOI  :  10.1186/s40364-023-00492-7

 received in 2023-03-04, accepted in 2023-04-29,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundComprehensive and integrative analysis of hepatocellular carcinoma (HCC) is important. In this study, we explored Taiwanese HCCs using multi-omics analyses.MethodsWe analyzed 254 HCCs by whole genome sequencing and total RNA sequencing, and then used bioinformatic tools to analyze genomic and transcriptomic alterations in coding and non-coding sequences to explore the clinical importance of each sequence.ResultsThe frequencies of the five most commonly mutated cancer-related genes were TERT, TP53, CTNNB1, RB1, and ARID1A. Genetic alteration frequencies influenced the etiology of HCC; some alterations were also correlated with clinicopathological conditions. Many cancer-related genes had copy number alterations (CNAs) and structure variants (SVs) that changed according to etiology and exhibited potential associations with survival. We also identified several alterations in histone-related genes, HCC-related long non-coding RNAs, and non-coding driver genes that may contribute to the onset and progression of HCC. Transcriptomic analysis revealed that 229 differentially expressed and 148 novel alternative splicing (AS) genes, as well as the presence of fusion genes, were associated with patient survival. Moreover, somatic mutations, CNAs, and SVs were associated with immune checkpoint gene expression and tumor microenvironment. Finally, we identified relationships among AS, immune checkpoint gene expression and tumor microenvironment.ConclusionsThis study shows that genomic alterations are associated with survival, including DNA-based and RNA-based data. Moreover, genomic alterations and their associations with immune checkpoint genes and the tumor microenvironment may provide novel insights for the diagnosis and treatment of HCC.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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