Discovery and characterization of tumor antigens in hepatocellular carcinoma for mRNA vaccine development

BACKGROUND: mRNA vaccines are emerging as new targets for cancer immunotherapy. However, the potential tumor antigens for mRNA vaccine design in hepatocellular carcinoma (HCC) remain to be elucidated. METHODS: Genetic and RNA-Seq data were obtained from TCGA and ICGC. Tumor-specific antigens (TSAs) were identified by differential expression, mutation status, HLA binding, antigen-presenting cell (APC) correlation, immune checkpoint (ICP) relevance and prognosis. Consensus clustering was used for patient classification. The molecular and immune status of TSAs and clustered patients, including prognostic ability, tumor microenvironment, tumor-related signature and tumor immune dysfunction and exclusion (TIDE), were further characterized. RESULTS: Five dysregulated and mutated TSAs were identified in HCC (TSA5): FXYD6, JAM2, GALNT16, C7, and CCDC146. Seven immune gene modules and five immune subtypes (IS1–IS5) of HCC were identified. The immune subtypes and TSA5-related modules showed distinct molecular, cellular and clinical characteristics. According to our study, IS1 patients may be suitable for vaccination.