鼻咽癌组织中高表达的GSDME对TME免疫浸润和患者预后的影响

Effect of high expression of GSDME in nasopharyngeal carcinoma tissues on immune infiltration of tumor microenvironment and patient prognosis

目的:探究细胞焦亡相关基因GSDME在鼻咽癌组织中的表达及其对肿瘤微环境(TME)和患者预后的影响。方法:从TCGA数据库获得548例鼻咽癌患者的基因表达数据及临床资料,运用R语言对GSDME进行差异表达分析、GO-KEGG富集分析;从人类蛋白质图谱(HPA)数据库中获取GSDME蛋白在鼻咽癌组织和相应癌旁组织中的表达数据,通过STRING数据库探究与GSDME相互作用的蛋白质网络;应用ss GSEA算法分析GSDME在鼻咽癌组织中的表达及其与24种免疫细胞浸润的相关性,运用Spearman法分析GSDME与免疫检查点分子的相关性,通过TISIDB数据库分析GSDME表达与细胞因子基因表达的相关性。单因素和多因素COX回归分析筛选预后风险因素,基于风险因素GSDME绘制预后预测列线图和校准图,根据GSDME的表达水平对鼻咽癌患者进行生存分析和风险分析。qPCR法验证中国人鼻咽癌组织中GSDME及4种趋化因子mRNA的表达。结果:数据库数据分析显示,与癌旁组织相比,鼻咽癌组织中GSDME呈高表达(P<0.01),GO-KEGG富集分析显示GSDME参与免疫反应、细胞焦亡相关信号通路,GSDME表达与免疫细胞浸润、细胞因子及免疫检查点分子表达等相关,q PCR检查结果验证了中国人鼻咽癌组织中GSDME呈高表达。GSDME表达量、N分期和M分期是鼻咽癌患者预后的风险因素,基于风险因素建立的列线图和校正图能较好地预测鼻咽癌患者OS,鼻咽癌组织中GSDME高表达的患者预后差。结论:GSDME在鼻咽癌癌组织中呈高表达且是患者预后风险因素,基于GSDME建立的列线图预测预后效能良好;GSDME高表达与TME免疫浸润有关,其可能是免疫治疗的潜在靶点。

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.