GSDMS are potential therapeutic targets and prognostic biomarkers in breast cancer

Pyroptosis is a new type of programmed death recently discovered,the GSDM family plays a crucial role in pyroptotic processes. Numerous studies have reported that GSDM family can either inhibit or promote tumor development; However, the mechanism of action in breast cancer is unclear. In this study, we employed diverse online databases to investigate the differential expression of GSDMS in breast cancer compared to para-cancer and transcriptional variations among molecular subtypes. Furthermore, we explored the association between GSDMS and clinical characteristics, assessed its prognostic value, examined gene alterations, investigated the relationship between subtypes and RFS, evaluated immune cell infiltration level, and analyzed the level of GSDMS methylation in breast cancer. We observed a significant upregulation of GSDMD in breast cancer, while GSDMB-E and PJVK exhibited low expression levels in this malignancy. GSDMB and GSDMC were highly expressed in HER2-positive breast cancer but showed low expression in triple-negative and luminal subtypes. GSDMD, GSDME, and PJVK displayed high expression specifically in the luminal phenotype of breast cancer while being downregulated in Her2+ and triple-negative subtypes. The expression pattern of GSDMS was closely associated with distinct clinical features. Missense mutation, deletion mutation, amplification, and deep deletion primarily accounted for alterations observed in the genes encoding GSDMA-E and PJVK with change rates ranging from 0.9% to 19%. Survival analysis revealed that elevated expressions of both GSDMD and PJVK were correlated with improved prognosis among breast cancer patients. Furthermore, the members of the GSDM family demonstrated strong associations with immune-infiltrating cells within the of breast cancer. DNA methylation analysis indicated lower levels along with decreased methylation patterns for GSDMC, GSDMD, and PJVK in breast cancer tissues; conversely increased methylation was observed for both GSDMA and GSDME. Our study systematically elucidates the expression and prognostic significance of GSDMS in breast cancer, as well as the potential prognostic implications of GSDMD and PJVK in breast cancer. These findings provide valuable guidance for clinicians regarding drug utilization.