Pancancer analysis of DNA damage repair gene mutations and their impact on immune regulatory gene expression
DNA damage plays a critical role in the development of numerous human diseases, including cancer, chronic inflammatory conditions, and premature aging. Genes involved in the DNA damage repair pathway are essential not only for maintaining the integrity of the genome but also for their involvement in immune responses through the regulation of antimicrobial peptides and ligands that activate immune receptors.
Various components of the DNA damage response, encompassing DNA damage sensors, transducer kinases, and effector proteins, possess the capacity to activate a wide range of immunological signaling pathways. While mutations in DNA damage repair genes are frequently observed in cancers, their precise impact on immune characteristics remains largely unclear. This study aimed to investigate how mutations in DNA damage repair genes influence the expression of immune regulatory genes, including those that stimulate or inhibit immune responses, as well as genes related to the major histocompatibility complex pathway.
To achieve this, we utilized gene expression data obtained from The Cancer Genome Atlas and mutation data available from cBioPortal. Our analysis focused on a set of 264 genes known to be involved in DNA damage repair and 66 genes with immune regulatory functions. These genes were subjected to clustering and categorization using Metascape, a comprehensive bioinformatics tool that employs enrichment-based analysis to group functionally related genes into distinct clusters.
The identified gene clusters were further validated through a thorough review of existing literature and the information contained within the GeneCards database. To quantify the changes in immune regulatory gene expression in response to mutations in DNA damage repair genes, we calculated a score to identify immune stimulators, inhibitors, and MHC-related genes that were differentially expressed.
Our analysis revealed the presence of both positive and negative correlations between the occurrence of mutations in DNA damage repair genes and the expression levels of immune modulatory genes. KP-457 These findings have the potential to inform the development of future cancer treatments based on the identification of relevant biomarkers and the application of immunotherapy strategies.