Integrative immunogenomic analysis reveals transcriptional and immune-related differences in hepatocellular carcinoma...

A comprehensive investigation of the neoantigen spectrum and immune infiltration in patients with hepatocellular carcinoma (HCC) is lacking. This study aimed to examine the molecular features correlating with better prognoses in HCC patients. 27 paired tumor and normal tissues from 27 HCC patients were collected and performed with whole-exome sequencing. The most frequently mutated gene in 27 HCC patients was TP53 (16/27, 59.26%). Based on the whole median disease-free survival (DFS), all patients were divided into 'long-term' (n = 14, median DFS = 318 weeks) and 'short-term' (n = 13, median DFS = 11 weeks) groups. RNA-seq was performed to compare differentially expressed genes, immune infiltration, and neoantigens. Immunohistochemistry was performed to evaluate the immune infiltration. There were no significant differences in tumor mutation burden, immune score, cytolytic activity score, or neoantigen load between two groups. Compared with the long-term group, significantly increased B lineage (P = 0.0463), myeloid dendritic cells (P = 0.0152), and fibroblast (P = 0.0244) infiltration levels were observed in the short-term group, in which genes involved in ribosome, proteasome, and ECM-receptor interaction pathways were also overexpressed. Additionally, 16 patients with tumor thrombus were explored to identify specific biomarkers for prognosis. We found that patients with tumor thrombus carrying TP53/ARID2 neoantigens had significantly longer DFS. In conclusion, higher B lineage, myeloid dendritic cells, and fibroblast infiltration levels might cause poor prognosis in the short-term group, which also showed higher expression of genes involved in ribosome, proteasome, and ECM-receptor interaction pathways. In patients with tumor thrombus, specific TP53/ARID2 neoantigens may be used as biomarkers toward personalized immunotherapy.