or mutations are associated with higher tumor mutational burden and worse survival in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most leading causes of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) have been proved to be beneficial for advanced HCC. Tumor mutational burden (TMB) is an important predictor for efficacy of ICIs. However, the genetic landscape of Chinese HCC patients and the association between TMB and frequently mutated genes of HCC remain unclear. Whole-exome sequencing data of 369 liver tumors from the Cancer Genome Altas (TCGA) and next generation sequencing (NGS) data of 657 liver tumors from Chinese clinical dataset were included. (61.8%) was the most frequently mutated gene in the Chinese cohort, followed by (17.2%), (13.7%), and (12.3%). The PI3K-Akt signaling (11.2%), the Rap1 signaling (8.1%), and Ras signaling (7.7%), were significantly mapped. mutations were significantly associated with higher TMB in both TCGA cohort ( = 0.0003) and Chinese cohort ( = 0.0005). And mutations were also associated with higher TMB in the TCGA and Chinese cohort ( = 0.0005 and 0.0010, respectively). Prognosis analysis performed in TCGA cohort revealed mutations were significantly associated with shorter overall survival (OS, median, 20.9 vs 61.7 months; HR, 2.22; = 0.0012). mutation was an independent risk factor affecting both OS (HR 1.58, = 0.0109) and PFS (HR 1.59, = 0.0027). The results suggest that or mutations are associated with higher TMB and a poor prognostic factor in HCC.