A Comprehensive Prognostic and Immunological Analysis of a New Three-Gene Signature in Hepatocellular Carcinoma

There are few reports on the role of genes associated with the mRNA expression-based stemness index (mRNAsi) in the prognosis and immune regulation of hepatocellular carcinoma (HCC). This study is aimed at analyzing the expression profile and prognostic significance of a new mRNAsi-based three-gene signature in HCC. This three-gene signature was identified by analyzing mRNAsi data from the Cancer Genome Atlas (TCGA) HCC dataset. The prognostic value of the risk score based on the three-gene signature was evaluated by Cox regression and Kaplan-Meier analysis and then verified in the International Cancer Genome Consortium (ICGC) database. Meanwhile, the correlations between the risk score and immune cell infiltration patterns, microsatellite instability (MSI), tumor mutation burden (TMB), immune checkpoint molecules, hypoxia-related genes, immunotherapy response, and compounds targeting the gene signature were explored, respectively. The results showed that compared with normal liver tissues, the mRNAsi score of HCC tissues was significantly increased. PTDSS2, MRPL9, and SOCS were the genes most related to mRNAsi in HCC tissues. Survival analysis results suggested the risk score based on the three-gene signature was an independent predictor of the prognosis for patients with HCC. The nomogram combining the risk score and pathological stage showed a good predictive ability for the overall survival of patients with HCC patients. Meanwhile, the risk score was significantly related to immune cell infiltration patterns, MSI, TMB, several immune checkpoint molecules, and hypoxia-related genes. In addition, the risk score was associated with the immunotherapy response, and fifteen potential therapeutic drugs targeting the three-gene signature were identified. Therefore, we propose to use this three-gene signature including PTDSS2, MRPL9, and SOCS as a potential prognostic biomarker for HCC.