An analysis of gasdermin family of genes in UCEC with respect to malignancy status, mutation percentages and histologic diagnosis

Abstract

Pyroptosis is a type of programmed lytic cell death mechanism associated with the activation of inflammasomes and inflammatory caspases, proteolytic cleavage of gasdermin proteins (GSDMA-E and PJVK), resulting in the formation of pores in cellular membranes such as plasma membrane and mitochondrial membranes. Here, I show that GSDMC expression was increased, GSDME (DFNA5) and PJVK (DFNB59) expression were decreased in uterine corpus endometrial carcinoma (UCEC) cells compared to normal non-malignant endometrial cells. Total percentage of patients affected by mutations in gasdermin family of genes was the highest in UCEC compared to other cancer types. The highest mutation percentage in UCEC patients among the members of the protein family was observed for GSDME which also showed the most significant difference in the mRNA expression among other family members between tumor and normal samples, possibly pointing to its relatively higher importance in the pathogenesis of UCEC. Gasdermin family of genes (except GSDMA) had higher transcript levels in serous endometrial adenocarcinoma than in endometrioid endometrial adenocarcinoma, demonstrating the histotype-dependent expression of the most of gasdermin family of genes in UCEC. Transcript levels of certain gasdermin family members also differed based on residual tumor status and histologic tumor grade; however, the expression of any gasdermin genes did not change depending on menopause status. This study suggests that a better mechanistic understanding of pyroptotic cell death in uterine corpus endometrial carcinoma might help identify novel therapeutic targets for the management of this gynecological malignancy.

Keywords

Uterine corpus endometrial carcinoma / Pyroptosis / Cell death / Gasdermin / Serous endometrial adenocarcinoma / Endometrioid endometrial adenocarcinoma / GSDME

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