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Abstract Background The accumulation of single nucleotide variants (SNVs) and the emergence of neoantigens can affect tumour proliferation and the immune microenvironment. However, the SNV-related immune microenvironment characteristics and key genes involved in hepatocellular carcinoma (HCC) are still unclear. We aimed to evaluate differences in the SNV-related immune microenvironment, construct a prognostic model and validate the key genes in vitro. Methods The categories of samples were defined by the expression of SNV score-related genes to evaluate the differences in mutational features, immune environment and prognosis. The survival model was constructed with survival-associated genes and verified in two independent test datasets. RCAN2, the key gene screened out for biofunction, was validated in vitro. Results IC2, among the three integrated clusters (IC1, IC2, IC3) classified by the 82 SNV score-related genes, was distinct from the rest in SNV score and immune cell infiltration, showing a better prognosis. Seven prognostic markers, HTRA3, GGT5, RCAN2, LGALS3, CXCL1, CLEC3B, and CTHRC1, were screened to construct a prognostic model. The survival model distinguished high-risk patients with poor prognoses in three independent datasets (log-rank P |
