GSDME upregulation predicts poor prognosis in gastric cancer

Pyroptosis is an inflammatory form of programmed cell death characterized by rapid plasma membrane rupture and the release of intracellular mediators, which distinguishes it from apoptosis and necrosis. Pyroptosis plays important roles in infection, autoimmunity, and cancer, highlighting its significance in immune homeostasis. Gasdermin E (GSDME), a key executor of pyroptosis, has been increasingly implicated in cancer. This study examined the expression and prognostic significance of GSDME in stomach adenocarcinoma (STAD).

GSDME was significantly upregulated in STAD tissue and associated with advanced stage and poor prognosis according to data from The Cancer Genome Atlas (TCGA) and the Xiantao Academic Online tool. Gene set enrichment analysis (GSEA) revealed that high GSDME expression was associated with genes enriched in immunosuppressive-related pathways in the TCGA-STAD cohort stratified by GSDME expression. Immune analysis revealed that GSDME expression was positively correlated with immune cell infiltration and the expression of immune checkpoint molecules, lymphocyte markers, immunomodulators, and major histocompatibility complex (MHC) molecules, as determined using R software and the Tumor-Immune System Interactions and Drug Bank (TISIDB). Western blotting and immunohistochemistry confirmed the elevated expression of GSDME in gastric cancer (GC) tissues. Functional analysis revealed that GSDME knockdown inhibited the proliferation and migration of AGS and MKN-45 GC cells while promoting cell death.

These findings suggest that GSDME may serve as a prognostic biomarker in GC and as a potential immune regulator.