基于生物信息学研究细胞周期蛋白依赖性激酶抑制因子2A基因与宫颈癌的关系及调控机制  

Relation of cyclin-dependent kinase inhibitor 2A gene with cervical cancer and its regulation mechanism:a bioinformatics study

作　　者：刘珍[1] 罗永金 胡晓霞[1] LIU Zhen;LUO Yong-jin;HU Xiao-xia(Department of Gynecology,the People′s Hospital of Guangxi Zhuang Autonomous Region,Nanning 530000,Guangxi,China;Faculty of Clinical Medicine,Guangxi Medical University,Nanning 530021,Guangxi,China)

机构地区：[1]广西壮族自治区人民医院妇科,广西南宁市530000 [2]广西医科大学临床医学院,广西南宁市530021

出　　处：《广西医学》2022年第12期1378-1383,共6页Guangxi Medical Journal

基　　金：国家自然科学基金(81660434);广西壮族自治区人民医院青年基金(QN2018-6)。

摘　　要：目的采用生物信息学方法分析细胞周期蛋白依赖性激酶抑制因子2A(CDKN2A)基因与宫颈癌的关系,并探讨其对宫颈癌潜在的调控机制。方法从GEO数据库中下载数据集GSE7803、GSE64217和GSE63514,并使用GEO2R软件筛选宫颈癌组织和正常组织之间的差异性表达基因,得到CDKN2A基因在宫颈鳞状细胞癌组织中的表达情况,并利用GEPIA数据库验证CDKN2A基因在宫颈鳞状细胞癌组织中的表达水平。通过DAVID在线工具针对差异性表达基因进行通路富集分析;利用STRING数据库和Cytoscape软件筛选与CDKN2A基因编码蛋白相互作用密切的蛋白。利用UALCAN在线工具分析CDKN2A基因表达与宫颈癌患者临床病理特征及预后的关系,以及宫颈癌组织中CDKN2A基因启动子甲基化水平。利用TIMER数据库分析CDKN2A基因表达水平与肿瘤免疫细胞浸润的相关性。利用ENCORI和mirDIP软件分析与CDKN2A基因有结合靶点的miRNA。结果共获得347个差异性表达基因,其中CDKN2A基因为上调基因;GEPIA数据库验证结果提示CDKN2A基因在宫颈鳞状细胞癌组织组织中呈高表达水平(P<0.05)。CDKN2A基因参与了细胞周期、p53信号通路及膀胱癌信号通路;共有22个蛋白与CDKN2A基因编码蛋白相互作用密切。淋巴结转移阳性宫颈癌患者中的CDKN2A基因表达水平高于淋巴结转移阴性者,CDKN2A基因高表达的宫颈癌患者的生存期短于低表达者(均P<0.05)。宫颈癌组织中CDKN2A基因启动子的甲基化水平较正常宫颈组织升高(P<0.05)。CDKN2A基因表达水平与巨噬细胞浸润水平呈负相关,与中性粒细胞、树突状细胞浸润水平呈正相关(均P<0.05)。共有9个miRNA可能与CDKN2A基因有结合靶点。结论CDKN2A基因与宫颈癌发生、发展密切相关,或可作为宫颈癌诊断及预后评估的潜在新分子标志物,并可为研究宫颈癌的免疫治疗提供新线索;该基因可能通过启动子区域甲基化或上游miRNA靶向调控在Objective To analyze the relation of cyclin-dependent kinase inhibitor 2A(CDKN2A)gene with cervical cancer employing bioinformatics method,and to explore its potential regulation mechanism on cervical cancer.Methods The data set of GSE7803,GSE64217 and GSE63514 was downloaded from the GEO database,and the differentially expressed genes between the cervical cancer tissues and the normal tissues were screened by the GEO2R software,acquiring the expression status of CDKN2A gene in the tissues of squamous cell carcinoma of the cervix,and the expression of CDKN2A gene in the tissues of squamous cell carcinoma of the cervix was verified using GEPIA database.The pathway enrichment analysis was conducted on differentially expressed genes by DAVID online tool;STRING database and Cytoscape software were used to screen the proteins closely interacted with CDKN2A gene encoded protein.The relation of CDKN2A gene expression with clinical pathological characteristics and prognosis in patients with cervical cancer,as well as the promoter methylation level of CDKN2A gene in the cervical cancer tissues were analyzed by UALCAN online tool.The correlation of CDKN2A gene expression with the infiltration of tumor immune cells was analyzed by TIMER database.The ENCORI and mirDIP softwares were used to analyze miRNAs with binding targets to CDKN2A gene.Results A total of 347 differentially expressed genes were acquired,thereinto CDKN2A gene was up-regulated gene;GEPIA database verification results hinted that CDKN2A gene expressed highly in the tissues of squamous carcinoma cells of the cervix(P<0.05).CDKN2A gene was involved in cell cycle,p53 signaling pathway,and bladder cancer signaling pathway,and 22 proteins were closely interacted with CDKN2A gene encoded protein in total.The expression of CDKN2A gene of cervical cancer patients with positive lymph nodes metastases was higher than that of cervical cancer patients with negative lymph nodes metastases,and cervical cancer patients with high expression of CDKN2A gene obtained a shorte

关 键 词：宫颈癌 细胞周期蛋白依赖性激酶抑制因子2A 临床病理特征 预后 启动子区域甲基化 微小RNA 生物信息学 

分 类 号：R737.33[医药卫生—肿瘤]