DNA Damage Repair Gene Mutations and Correlations with Immune Regulatory Gene Expression in Pancancer

DNA damage is the root cause of many human disorders, including chronic inflammatory diseases, cancer, and early ageing. The DDR can also help the immune system by boosting the production of antimicrobial peptides and ligands for immune cell receptors. Different immunological signals are activated by various DDR components, including DNA damage sensors, transducer kinases, and effectors. A tight functional link and coordination between DDR and immune defence protect against harmful microorganisms and control tumours. Although DNA damage repair gene mutations are frequently found in cancer, very little is understood about how DDR mutations influence immunological traits. We explored the response of immune regulatory genes, including known stimulators, inhibitors and MHC pathway-related genes, to mutations in genes related to DNA damage repair mechanisms. In this study, we used pancancer gene expression data from the TCGA database and gene mutation data uploaded to the cBioPortal. A total of 275 genes related to DDR and 67 genes related to immune regulatory functions were clustered and categorised into different groups and validated through the literature. The dataset was segregated on the basis of mutations in known DDR genes, and changes in the relative expression of immune regulatory genes were scored to identify immune stimulators, inhibitors, and MHC pathway-related genes that were differentially regulated in response to a DDR mutation. We found positive correlations between DNA damage repair, gene mutations, immune stimulators, inhibitors, and MHC pathway-related gene expression. This study will lead to the identification of important building blocks for any future cancer treatment based on biomarkers and immunotherapy.