Objective: The Gasdermin (GSDM) protein family plays a pivotal role in inducing pyroptosis, a form of programmed cell death. Pyroptosis is closely associated with the initiation, progression, and prognosis of various cancer types. However, the relationship between GSDMS expression and breast cancer, as well as the underlying molecular mechanisms, remains insufficiently characterized.

Materials and Methods: In this study, we conducted a comprehensive analysis of GSDMS expression in breast cancer using multiple databases, including UALCAN, BC-GenExMiner, OncoPrint, TIMER, Kaplan-Meier, TIMER 2.0, cBioPortal, DiseaseMeth 3.0, and OncoLnc. Furthermore, the analysis was confirmed online using the R package.

Results: Except for GSDMA, all other GSDMS family members exhibited differential expression between breast tumor tissues and adjacent normal tissues. The expression patterns of these genes were significantly correlated with distinct clinical features of breast cancer. Genetic alterations, including missense mutations, deletions, amplifications, and deep deletions, were the primary contributors to changes in the GSDMA-E and PJVK genes, with mutation frequencies ranging from 0.90% to 19.00%. Elevated expression levels of GSDMD and PJVK were associated with improved patient prognosis. Additionally, members of the GSDM family showed strong correlations with immune cell infiltration, particularly lymphocytes, within breast cancer tissues. DNA methylation analysis revealed hypomethylation of GSDMC, GSDMD, and PJVK in breast cancer tissues, whereas hypermethylation was observed for GSDMA and GSDME.

Conclusions: Our findings indicate that GSDMD and PJVK are potential therapeutic targets and prognostic biomarkers in breast cancer. This study enhances our understanding of the roles of GSDMS family members in breast cancer and provides critical insights for clinicians in the development of targeted therapies and treatment strategies.