Prognostic and Immunological Role of Gasdermin E in Pan-Cancer Analysis

Abstract

Despite accumulating cell- or animal-based experiments providing the relationship between Gasdermin E (GSDME) and human diseases, especially in malignant cancers, no pan-cancer analysis about the function of GSMDE in cancer management can be available up to date. Our research, for the first time, explored the potential carcinogenic role of GSDME across 33 tumors from the public platform of TCGA (The cancer genome atlas) database. GSDME is highly expressed in most malignant cancers, and obvious relationship exists between GSDME level and survival prognosis of cancer patients. The expression of GSDME was statically associated with the cancer-associated fibroblast infiltration in diverse cancer types, such as BLCA, CHOL, GBM, KIRC, LIHC, MESO, STAD, and UCEC. Furthermore, pyroptosis, sensory perception of sound, and defense response to bacterium were involved in the functional mechanisms of GSDME expression from GO analysis. Last but not the least, in vitro experiments were also performed to identify GSDME-induced pyroptosis. Our first pan-cancer analysis of GSDME not only broadens the understanding of the carcinogenic roles of GSDME but also provides a promising therapeutic strategy for benefiting an increasing number of cancerous patients based on GSDME-induced pyroptosis.

Keywords: gasdermin E; immune infiltrate; pan-cancer analysis; pyroptosis; survival analysis.

Figure 1

(A) The expression difference of the GSDME in diverse cancers or certain cancer subtypes was analyzed via TIMER2 algorithm. (B) For ACC, DLBC, LAML, LGG, OV, SARC, SKCM, TGCT, THYM, and UCS in the TCGA database, the adjacent normal tissues of the GTEx project were included as controls. The box plots were then graphed. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 2

(A) Expression status of GSDME in various pathological stages (stage I, stage II, stage III, and stage IV) of BLCA, ESCA, KICH, KIRC, KIRP, READ, and UCEC. (B) Correlation of GSMDE expression with overall survival and disease-free survival across different TCGA cancers.

Figure 3

(A) Alteration characterizes of GSDME in diverse cancers in TCGA project. (B) The potential relationship between mutation status and disease-free, disease-specific, and progression-free survival from the cBioPortal tool.

Figure 4

(A) The potential correlation between GSDME expression and immune cell infiltration of cancer-associated fibroblasts in all TCGA cancers. (B) The scatter plots of related cancers generated by one algorithm, including BLCA, CHOL, GBM, KIRC, LIHC, MESO, STAD and UCEC.

Figure 5

(A) The available determined GSDME-related proteins from the STRING website. (B) The correlation between GSDME and selected binding genes, such as PEZ1, GNA12, MAP4, SEPT7 TPST1, and TBL2 from the GEPIA2 tool. (C) The corresponding heatmap data of different cancer types are graphed in detail. (D) GO analysis was displayed based on the GSDME-binding genes. (E) The typical morphology of pyroptosis in MCF-7 cells after apoptotic stimuli. Error bar: 200 nm.