Exploring a new candidate gene, MSH6, related to hepatocellular carcinoma based on bioinformatics

Abstract Background: The expression of MSH6 is generally increased in many tumors, but its role in hepatocellular carcinoma (HCC) is unclear. The purpose of this study was to evaluate the expression of the DNA mismatch repair protein MSH6 in HCC and its impact on the prognosis of HCC patients and to clarify the mechanism by which MSH6 affects the malignant behavior of HCC. Methods: R (4.2.1) software was used to obtain the expression level and clinical data of MSH6 mRNA in cancer tissues and adjacent tissues of patients with hepatocellular carcinoma from the Cancer Gene Atlas (TCGA) platform.The expression difference of MSH6 mRNA in normal and tumor tissues was compared, and GEO data were used to verify the above results. MSH6-related genes were analyzed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and GSEA. Kaplan‒Meier survival analysis, receptor operating characteristic (ROC) curves, and nomograms confirmed the predictive value of MSH6 for the clinical outcome of patients with HCC. Results: Compared with the adjacent tissues, the expression level of MSH6 mRNA in cancer tissues from HCC patients was significantly higher. MSH6 plays a role in pathways related to digestion, the antimicrobial humoral response, and the G protein-coupled receptor signaling pathway. In HCC samples, high expression of MSH6 tended to have significant relationships with hormone activity, receptor-ligand activity, and G protein-coupled receptor binding. Kaplan‒Meier survival analysis showed that the prognosis of patients with lower MSH6 mRNA expression was significantly better than that of patients with higher MSH6 mRNA expression. The calibration plot shows that the MSH6 model has an effective performance for hepatocellular carcinoma prediction. Conclusion: MSH6 plays an important role in the pathogenesis and progression of HCC and can be used as an indicator to evaluate and predict the prognosis and survival of hepatocellular carcinoma patients.