GSDME Is Related to Prognosis and Response to Chemotherapy in Oral Cancer

Gasdermin E (GSDME), as the major executive protein of pyroptosis, has been considered to be linked to antitumor immunity in recent years. However, the role of GSDME in oral squamous cell carcinoma (OSCC) remains to be elucidated. Here, by using a human OSCC tissue microarray, human OSCC tissue, and Tgfbr1/Pten conditional knockout mice, we found that GSDME was strongly expressed in OSCC and that GSDME expression in primary tumors was higher than that in metastatic lymph nodes. In addition, GSDME expression in OSCC was positively related to better prognosis. Moreover, GSDME-mediated pyroptosis occurred upon stimulation with chemotherapy drugs, and functional knockdown of GSDME attenuated the cisplatin-induced antitumor effect. Consistent with these results, bioinformatic analysis indicated that GSDME expression was positively correlated with the sensitivity of a number of antitumor drugs approved by the US Food and Drug Administration. Inhibition of GSDME expression by small interfering RNA in SCC7 cells significantly increased the expression of the cancer stem cell markers, CD44 and ALDH1. Furthermore, multiplexed immunohistochemistry and flow cytometry indicated that the expression of GSDME positively correlated with tumor-infiltrating CD8⁺ T cells, granzyme B, and M1 phenotype macrophages. Collectively, these findings demonstrated that GSDME is a potential positive prognostic factor of OSCC, and GSDME-mediated pyroptosis induced by chemotherapy plays a role in antitumor response.