The effect of the TP53 and RB1 mutations on the survival of hepatocellular carcinoma patients with different racial backgrounds

Abstract

Background: Racial disparities in the survival of patients with hepatocellular carcinoma (HCC) exist. Gene mutations have a profound effect on carcinogenesis, are easily affected by environment and etiology factors, and may result in survival divergences among patients with different racial backgrounds. This report explores the effects of gene mutations on the survival of American Caucasians and Asian patients. Methods: The sequencing and clinical data of 336 HCC patients were obtained from The Cancer Genome Atlas (TCGA) database. The sequencing data was subject to gene mutation profiling, and an analysis of immune cell infiltration was conducted. A multivariate analysis was performed to assess the independent effects of gene mutations on patients’ overall survival (OS) and disease-free survival (DFS). Results: Asian HCC patients had a significantly higher level of TP53 mutation frequency than Caucasian HCC patients (Asian vs. Caucasian, 39% vs. 23%; P=0.003). The TP53 mutation was associated with shorter OS [hazard ratio (HR), 2.33; 95% confidence interval (CI), 1.36–3.97; P=0.002] and DFS (HR, 2.2; 95% CI, 1.38–3.51; P<0.001) in Caucasian HCC patients, but had no effect on Asian HCC patients’ survival. Compared to Asian HCC patients, Caucasian HCC patients with the TP53 mutation had a decreased proportion of infiltrating M2 macrophages and activating natural killer (NK) cells, and an increased proportion of follicular helper T cells. The RB1 mutation was associated with shorter OS (HR, 3.37; 95% CI, 1.73–6.57; P<0.001) in Asian HCC patients, and shorter DFS (HR, 2.11; 95% CI, 1.15–3.88; P=0.017) in Caucasian HCC patients. Asian HCC patients with the RB1 mutation had a decreased proportion of infiltrating CD8 T cells. Conclusions: The effects of the TP53 and RB1 mutations on survival differ among Asian and Caucasian HCC patients.