The prognostic value of genetic alterations of gasdermin (GSDM) family genes in breast cancer.

e13006 Background: Breast cancer (BC) is the most commonly diagnosed cancer in 2021, with an estimated 2.9 million new cases (31%) and the second leading cause of cancer death in women. Gasdermins are encoded by six paralogous genes: GSDMA, GSDMB, GSDMC, GSDMD, GSDME (also known as DFNA5) and DFNB59 (also known as pejvakin, PJVK). They play a key role in pyroptosis. Few studies addressing the association between genetic alterations in the GSDM family genes and breast cancer prognosis have been reported up to now. Methods: We used a public cancer research platform named cBioPortal to analyze a cohort of 1983 breast cancer samples. We defined overall survival (OS) as the time between the procedure date when the tumor specimen was collected and the date of death or last follow-up visit. We compared the survival curves of two groups using Kaplan-Meier method and log-rank tests. The statistical significance level was set to 5% (p < 0.05). Results: These genes were found in 685 (34.5%) samples with various genetic alterations, including missense mutation, splice mutation, truncating mutation, structural variant, amplification, deletion. GSDMC was the most frequently altered gene (18%), followed by GSDMD (17%), GSDMB (11%), GSDMA (10%), GSDME (2.5%), and PJVK (0.7%). Based on the result, patients were divided into the GSDM mutation and non-GSDM mutation group. The median OS of the GSDM mutation group was 124.57 months (Table), which is significantly shorter than the OS of the non-GSDM mutation group (log-rank test p = 5.64e-7). Conclusions: To our best knowledge, this analysis is the first investigation to evaluate the association between prognostic value and genetic alterations in GSDM family genes in breast cancer patients. Our investigation shows that genetic alterations in GSDM family genes can be used to predict poor prognosis in breast cancer patients. Further studies are warranted to verify and expand on these findings.[Table: see text]