Background: Gasdermins (GSDMs) are a class of proteins related to pyrolysis and in humans, consist of GSDMA, GSDMB, GSDMC, GSDMD, DFNA5, and DFNB59. The inflammatory factors and cell contents released during pyrolysis can recruit immune cells and change the microenvironment. However, to date, there is a paucity of studies examining the relationship between GSDMs and the immune microenvironment in tumors. Therefore, this current report analyzed the expression of GSDM genes in tumors and their relationship with the immune microenvironment.
Methods: Apply GSCALite and GEPIA2 online analysis tools to analyze the gene expression levels and the Single nucleotide variant (SNV), copy number variation (CNV), and methylation characteristics of GSDM genes respectively. Use R software or TISIDB online analysis tool to carry out the correlation analysis required in the article. Furthermore, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to examine the role of these GSDM genes in various cancers.
Results: The results demonstrated that CNV can cause an increase in GSDM gene expression, and methylation can inhibit GSDM gene expression. The elevated expression of GSDMA, GSDMB, GSDMC, GSDMD, and DFNA5 in some or most tumors was often accompanied by elevated immune scores, increased immune cell infiltration, and high expression of major histocompatibility complex (MHC) molecules, chemokines and their receptors, and immune checkpoint-related genes. However, DFNB59 was often negatively correlated with these indicators in tumors. GSDMD was the most highly expressed GSDM protein in various normal tissues and tumors, and showed the strongest correlation with immune microenvironment-related genes. Moreover, the methylation of GSDMD was accompanied by low immune cell infiltration, low expression of MHC molecule-related genes, low expression of chemokines and receptor-related genes, and low expression of immune checkpoint-related genes.
Conclusions: Therefore, the expression of GSDM-related genes is associated with the tumor immune microenvironment. The GSDM genes, especially GSDMD, may be used as therapeutic targets to predict or change the tumor microenvironment and as biomarkers to predict the therapeutic efficacy of immune checkpoint inhibitors.
Keywords: Gasdermins (GSDMs); immune cell infiltration; immune checkpoint; immune microenvironment; pan-cancer.
2021 Translational Cancer Research. All rights reserved.