A Pan-Cancer Analysis of the Oncogenic Roles of RAD51 in Human Tumors

Abstract

Objective. RAD51 homolog 1 (RAD51) plays significant roles in DNA damage repair and apoptosis. These pathways are tightly associated with tumor initiation and progression. To unravel the roles of RAD51 in oncogenesis and progression of different cancers, herein, a comprehensive analysis of the RAD51 was carried out using multiomics datasets of 33 cancers. Methods. Raw data were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. We analyzed the correlation between RAD51 expression and drug response using datasets from CellMiner. Next, clinical characteristics and prognostic values of RAD51 were conducted based on TCGA data. The correlation between RAD51 expression and tumor immune infiltration was explored. This was followed by gene set enrichment analysis by Rsoftware. In addition, pan-cancer analysis was conducted to investigate genetic and epigenetic alterations, respectively. Results. RAD51 was upregulated in most tumors, and this was associated with poor overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS). The expression level of RAD51 is significantly associated with the IC50 of multiple antitumor drugs and the proportion of stromal and immune components in tumor microenvironment (TME). Moreover, RAD51 expression showed a positive relationship with multiple key immune checkpoint and immunosuppressive genes, including death-ligand 1 (PD-L1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), CD28, and several TNF-related immune genes. Gene set enrichment analysis uncovered that RAD51 correlated with cell cycle, cell division, and immune system pathways in diverse cancers. Our results revealed a strong link between RAD51 expression and microsatellite instability (MSI) or tumor mutation burden (TMB). Conclusions. Our pan-cancer analysis provides a comprehensive overview of the roles of RAD51 in multiple human cancers and infers that RAD51 has the potential as a biomarker for progression and immune infiltration of different tumor types.