%0 Journal Article
%T Integrated genomic analyses of hepatocellular carcinoma.
%A Chang YS
%A Tu SJ
%A Chen HD
%A Hsu MH
%A Chen YC
%A Chao DS
%A Chung CC
%A Chou YP
%A Chang CM
%A Lee YT
%A Yen JC
%A Jeng LB
%A Chang JG
%J Hepatol Int
%V 17
%N 1
%D Feb 2023
%M 36472800
%F 9.029
%R 10.1007/s12072-022-10455-z
%X <B>BACKGROUND: </B>Genomic alterations play important roles in the development of cancer. We explored the impact of protein-coding genes and transcriptomic changes on clinical and molecular alterations in Taiwanese hepatocellular carcinoma (HCC) patients.<BR><B>METHODS: </B>We analyzed 147 whole-exome sequencing and 100 RNA sequencing datasets of HCC and compared them with The Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma cohort and develop a panel of 81 apoptosis-related genes for molecular classification.<BR><B>RESULTS: </B>TERT (50%), TP53 (25%), CTNNB1 (14%), ARID1A (12%), and KMT2C (11%) were the most common genetic alterations of cancer-related genes. ALDH2 and KMT2C mutated at much higher frequencies in our cohort than in TCGA, whereas CTNNB1 was found only in 14% of our Taiwanese patients. A high germline mutation rate of ALDH2 in the APOBEC mutational signature and herb drug-related aristolochic acid-associated signature was also observed. Groups A and B of HCC were identified when we used apoptosis-related genes for molecular classification. The latter group, which had poorer survival outcomes, had significantly more aDC, CD4+ Tem, macrophages M2, NKT, plasma cells, and Th1 cells, and less CD4+ memory T cells, CD8+ Tcm, cDC, iDC, and Th2 cells, as well as more inter-chromosome fusion genes. Metatranscriptomic analysis revealed 54 cases of HBV infection. Moreover, we found that the main target gene of HBV integration is ALB.<BR><B>CONCLUSIONS: </B>Unique genomic alterations were observed in our Taiwanese HCC patients. Molecular classification using apoptosis-related genes could lead to new therapeutic approaches for HCC.