Comprehensive Analysis of Granzymes and Perforin Family Genes in Pan-Cancer

Abstract Cancer remains a significant global health concern, with immunotherapies emerging as promising treatments. This study explores the role of perforin-1 (PRF1) and granzymes-A, -B and -K (GZMA, GZMB and GZMK) in cancer biology, focusing on their impact on tumor cell death and immune response modulation. Through comprehensive genomic analysis across various cancer types we explored the differential expression, mutation profiles, and methylation patterns of these genes, providing insights into their potential as therapeutic targets. Furthermore, we investigated their association with immune cell infiltration and pathway activation within the tumor microenvironment in each cancer. Our findings reveal distinct expression patterns and prognostic implications of PRF1, GZMA, GZMB and GZMK across different cancers, highlighting their multifaceted roles in tumor immunity. We found increased immune infiltration across all tumor types and significant correlations between the genes of interest and cytotoxic T cells, as well as the greatest significant survival outcomes in breast cancer. We also show that granzymes and perforin-1 are significantly associated with indicators of immunosuppression and T cell dysfunction within patient cohorts. In skin melanoma, glioblastoma, kidney and bladder cancer we found significant correlations between the genes of interest and patient survival after receiving immune-checkpoint inhibition therapy. Additionally, we identified potential associations between the mRNA expression levels of these genes and drug sensitivity. Overall, this study enhances our understanding of the molecular mechanisms underlying tumor immunity and provides valuable insights into the potential therapeutic implications of PRF1, GZMA, GZMB and GZMK in cancer treatment.