Replication Protein A in Cancer: A Pan-Cancer Analysis Focusing on Lower-Grade Glioma and Liver Hepatocellular Carcinoma

Background Replication Protein A (RPA) is an important single-stranded DNA-binding complex that is crucial for DNA repair and thereby maintains genome stability. However, a comprehensive pan-cancer analysis revealing the role of the RPA gene family in cancer progression remains lacking. Methods In this study, we performed a comprehensive pan-cancer analysis of the RPA gene family. Briefly, gene expression analysis, genetic mutation analysis, survival prediction analysis, functional annotation, tumor microenvironment analysis, and drug sensitivity analysis of RPA genes were performed using the TCGAplot R package and various web tools, including GEPIA3, TIMER3, HPA, cBioPortal, UALCAN, and GSCALite. TCGA, CPTAC, GTEx, GDSC, and CTRP datasets were utilized for various analysis. All statistical analysis were performed using R. Results The results revealed that RPA genes were overexpressed across multiple cancer types, including liver hepatocellular carcinoma (LIHC), and brain lower-grade glioma (LGG). High expression of RPA genes was associated with worse prognosis in LGG and LIHC. Correlation analysis with immunomodulators revealed positive correlations. Poor prognosis, along with a positive correlation, indicates an immune-inflamed yet immunosuppressive tumor microenvironment. TMB/MSI analysis revealed a very weak positive correlation, indicating low immunogenicity; however, drug sensitivity analysis showed a strong positive correlation, indicating susceptibility to targeted therapeutic strategies. Conclusions Overexpression of RPA genes was significantly associated with a worse prognosis, an immunosuppressive environment, and a weak immunotherapeutic response in liver cancers and gliomas. Furthermore, RPA expression was sensitive to various drugs, such as doxorubicin; hence, RPA genes may serve as potential prognostic and therapeutic biomarkers in LGG and LIHC.