Identification of tumor antigens and immune subtypes of hepatocellular carcinoma for mRNA vaccine development.

Abstract

mRNA vaccines have been investigated in multiple tumors, but limited studies have been conducted on their use for hepatocellular carcinoma (HCC). To identify candidate mRNA vaccine antigens for HCC and suitable subpopulations for mRNA vaccination. Gene expression profiles and clinical information of HCC datasets were obtained from International Cancer Genome Consortium and The Cancer Genome Atlas. Genes with somatic mutations and copy number variations were identified by cBioPortal analysis. The differentially expressed genes with significant prognostic value were identified by Gene Expression Profiling Interactive Analysis 2 website analysis. The Tumor Immune Estimation Resource database was used to assess the correlation between candidate antigens and the abundance of antigen-presenting cells (APCs). Tumor-associated antigens were overexpressed in tumors and associated with prognosis, genomic alterations, and APC infiltration. A consensus cluster analysis was performed with the Consensus Cluster Plus package to identify the immune subtypes. The weighted gene coexpression network analysis (WGCNA) was used to determine the candidate biomarker molecules for appropriate populations for mRNA vaccines. AURKA, CCNB1, CDC25C, CDK1, TRIP13, PES1, MCM3, PPM1G, NEK2, KIF2C, PTTG1, KPNA2, and PRC1 were identified as candidate HCC antigens for mRNA vaccine development. Four immune subtypes (IS1-IS4) and five immune gene modules of HCC were identified that were consistent in both patient cohorts. The immune subtypes showed distinct cellular and clinical characteristics. The IS1 and IS3 immune subtypes were immunologically "cold". The IS2 and IS4 immune subtypes were immunologically "hot", and the immune checkpoint genes and immunogenic cell death genes were upregulated in these subtypes. IS1-related modules were identified with the WGCNA algorithm. Ultimately, five hub genes (RBP4, KNG1, METTL7A, F12, and ABAT) were identified, and they might be potential biomarkers for mRNA vaccines. AURKA, CCNB1, CDC25C, CDK1, TRIP13, PES1, MCM3, PPM1G, NEK2, KIF2C, PTTG1, KPNA2, and PRC1 have been identified as candidate HCC antigens for mRNA vaccine development. The IS1 and IS3 immune subtypes are suitable populations for mRNA vaccination. RBP4, KNG1, METTL7A, F12, and ABAT are potential biomarkers for mRNA vaccines.