Effect of high expression of GSDME in nasopharyngeal carcinoma tissues on immune infiltration of tumor microenvironment and patient prognosis
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Abstract:
Objective: To explore the impact of pyroptosis related gene GSDME on the prognosis of patients with nasopharyngeal carcinoma and its interaction with the immune microenvironment. Methods: Gene expression profile and clinical data of 548 patients with nasopharyngeal carcinoma were obtained from TCGA database. Differential expression analysis and GO-KEGG enrichment analysis of GSDME were conducted using R language. Immunohistochemical maps of GSDME protein in nasopharyngeal carcinoma tissues and corresponding para-carcinoma tissues were obtained from The Human Protein Atlas database. The interacting proteins of GSDME were explored by using STRING database. The correlation between GSDME expression and infiltration of 24 kinds of immune cells in nasopharyngeal carcinoma tissues was analyzed by ssGSEA algorithm, the correlation between GSDME expression and immune checkpoint molecules was analyzed by Spearman method, and the correlation between GSDME expression and cytokine expression was analyzed by using TISIDB database. Univariate and multivariate COX regression analyses were used to screen the risk factors for prognosis, based on which, the nomogram and calibration curve were drawn. Survival analysis and risk analysis were performed in nasopharyngeal carcinoma patients based on GSDME expression levels. The mRNA expression of GSDME and four chemokines in Chinese nasopharyngeal carcinoma tissues was verified by qPCR. Results: Analysis of database data showed that GSDME was highly expressed in nasopharyngeal carcinoma tissues compared with paraneoplastic tissues (P<0.01), GO-KEGG enrichment analysis showed that GSDME was involved in immune response, cell pyroptosis-related signaling pathways, and GSDME expression was correlated with immune cell infiltration, cytokine and immune checkpoint molecule expression. qPCR examination of Chinese nasopharyngeal carcinoma tissues verified the bioinformatics predictions; GSDME expression, N stage and M stage were risk factors for the prognosis of nasopharyngeal carcinoma patients, and the nomogram and calibration curve based on risk factors could better predict the OS of nasopharyngeal carcinoma patients, and patients with high GSDME expression in nasopharyngeal carcinoma tissues had poor prognosis. Conclusion: GSDME is highly expressed in nasopharyngeal carcinoma tissues and is associated with patient's poor prognosis. High GSDME expression is associated with the pro-cancer effect of the immune microenvironment in nasopharyngeal carcinoma, which may be a potential target for immunotherapy.