焦孔素蛋白E与宫颈癌相关性分析

Correlation Analysis of Gasdermin E and Cervical Cancer

目的分析焦孔素蛋白E(gasdermin E,GSDME)与宫颈癌发生、发展的相关性。方法采用HPA数据库和GE-PIA2网站分析宫颈癌组织与正常宫颈组织中GSDME基因和蛋白表达差异;GEPIA2和KMplotter网站分析GSDME基因表达与宫颈癌病理分期、生存预后的相关性;eBioPortal网站分析宫颈癌组织中GSDME基因突变;TIMER2网站和R语言分析宫颈癌组织中GSDME与免疫细胞浸润的相关性;基因富集分析GSDME在宫颈癌发展过程中的生物学功能。实时荧光定量聚合酶链反应(real-time quantitative polymerase chain reaction,RT-qPCR)和Westernblot法检测宫颈癌细胞中GSDME的转录和翻译。结果与正常宫颈组织比较,宫颈癌组织中GSDMEmRNA和蛋白质均呈低表达(P<0.05);生存分析显示,GSDME基因高表达可能与宫颈癌患者不良预后有关;GSDME在宫颈鳞状细胞癌中存在0.36%的基因突变;宫颈癌组织中GSDME基因高表达与B淋巴细胞浸润呈显著负相关,与肥大细胞浸润呈显著正相关(P<0.001);宫颈癌组织中GSDME高表达与谷胱甘肽过氧化物酶活性.mRNA修饰以及角蛋白丝生成等生物学功能呈显著负相关(P<0.001);RT-qPCR和Western blot法检测结果显示,人类乳头瘤病毒(human papilloma virus,HPV)阳性或阴性宫颈癌细胞中均能检测到GSDME的转录和蛋白质的表达。结论GSDME可能是宫颈癌相关的一个危险因子,GSDME与宫颈癌相关性分析为后续基于GSDME的宫颈癌靶向治疗提供了新视角。

Objective To analyze the correlation between gasdermin E(GSDME)and the occurrence and development of cervical cancer.Methods HPA database and GEPIA2 online website were used to analyze the differential expression of GSDME gene and protein between cervical cancer tissues and normal cervical tissues.GEPIA2 and KM plotter online website was used to analyze the correlation be-tween GSDME gene expression and the pathological staging,survival and prognosis of cervical cancer.cBioPortal online website was used to analyze the GSDME gene mutation in cervical cancer tissues.TIMER2 online website and R-package were used to analyze the correla-tion between GSDME and immune infiltration in cervical cancer tissues.Gene set enrichment analysis was used to analyze the biological function of GSDME in development of cervical cancer.Real-time quantitative polymerase chain reaction(RT-qPCR)and Western blot were used to verify the transcription and translation of GSDME in cervical cancer cell lines.Results Compared with normal cervical tis-sues,the expression of GSDME mRNA and protein in cervical cancer tissues was lower(P<0.05).Survival analysis showed that the high expression of GSDME gene may be associated with poor prognosis of cervical cancer patients.0.36%of CSDME amplification muta-tion was found in cervical squamous cell carcinoma.There was significant negative correlation between high expression of GSDME gene and B lymphocyte infiltration,whereas a significant positive correlation between high GSDME gene and mast cell infiltration in cervical cancer tissues(P<0.05).The high expression of GSDME in cervical cancer exhibited a significant negative correlation with glutathione peroxidase activity,mRNA modification,keratin filament,and other biological functions(P<O.O01).RT-qPCR and Western blot con-firmed that the transcription and protein expression of CSDME could be detected in both human papilloma virus(HPV)positive and nega-tive cervical cancer cells.Conclusion GSDME may be a risk factor related to cervical cancer,and the correlation analysis between GS-DME and cervical cancer provides a new perspective for the follow-up targeted treatment of cervical cancer based on GSDME.