Pan-cancer analysis reveals the expression, genetic alteration and prognosis of pyroptosis key gene GSDMD

Int Immunopharmacol. 2021 Dec;101(Pt A):108270. doi: 10.1016/j.intimp.2021.108270. Epub 2021 Oct 29.

Abstract

Background: Gasdermins (GSDMs)-mediated pyroptosis is widely involved in activating anti-tumor immunity and suppressing tumor growth. However, whether gasdermin D (GSDMD)-mediated pyroptosis affects patient prognosis in pan-cancer remains unknown.

Methods: We performed analyses of the RNA expression, genetic alteration, prognosis and immune infiltration of GSDMD in pan-cancer. In order to explore the relationship between pyroptosis and tumors, we calculated the correlation between GSDMD and pyroptosis key genes in pan-cancer. We also investigated the enrichment pathway of GSDMD-related genes.

Results: GSDMD was differentially expressed in the vast majority of cancer, and could be used as a prognostic marker in adrenocortical carcinoma (ACC), kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), skin cutaneous melanoma (SKCM) and rectum adenocarcinoma (READ). Strong evidence indicated the significant correlation of GSDMD with almost all immune checkpoints and immune cells. Pyroptosis-related genes strongly associated with GSDMD in ACC, KIRC, LGG, LIHC and SKCM, suggesting that GSDMD-mediated pyroptosis might play a critical role in the five cancers.

Conclusion: All the evidence supported the potential role of GSDMD-mediated pyroptosis in cancer. Our results provided new insights into GSDMD as a prognostic marker and potential therapeutic target for cancer.

Keywords: Cancer; GSDMD; Genetic alteration; Immune infiltration; Prognosis; Pyroptosis.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Datasets as Topic
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / mortality
  • Phosphate-Binding Proteins / antagonists & inhibitors
  • Phosphate-Binding Proteins / genetics*
  • Phosphate-Binding Proteins / metabolism
  • Pore Forming Cytotoxic Proteins / antagonists & inhibitors
  • Pore Forming Cytotoxic Proteins / genetics*
  • Pore Forming Cytotoxic Proteins / metabolism
  • Prognosis
  • Pyroptosis / drug effects
  • Pyroptosis / genetics*
  • Pyroptosis / immunology
  • Survival Analysis

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • GSDMD protein, human
  • Phosphate-Binding Proteins
  • Pore Forming Cytotoxic Proteins