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Updated: Aug 18, 2025
Mass Cytometry Analysis of Systemic and Local Immune Responses in Hepatocellular Carcinoma
Published on: April 25, 2025
Integrated genomic analyses of hepatocellular carcinoma
Ya-Sian Chang1,2,3,4, Siang-Jyun Tu1,2,3, Hong-Da Chen1,2,3
1Center for Precision Medicine, China Medical University Hospital, 2 Yuh-Der Road, Taichung, 404, Taiwan.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
Unique genomic alterations were observed in our Taiwanese HCC patients. Molecular classification using apoptosis-related genes could lead to new therapeutic approaches for HCC.
