Integrated bioinformatics analysis of expression, related signal pathways, and prognostic significance of CCNA2 in hepatocellular carcinoma
- Author:
- No author available
- Journal Title:
- World Chinese Journal of Digestology
- Issue:
- 24
- DOI:
- 10.11569/wcjd.v27.i24.1490
- Key Word:
- 肝细胞癌;TCGA数据库;CCNA2基因;信号通路;预后
Abstract： 背景 肝细胞癌(hepatocellular carcinoma,HCC)是消化系统常见恶性肿瘤,预后较差.本文拟采用生物信息学方法探讨CCNA2基因在HCC中的表达情况,及其作为HCC患者预后分子标志物的可行性.同时,采用免疫组织化学法对CCNA2生物信息分析结果进行验证.目的 探讨CCNA2在HCC中的表达,相关信号通路及与患者预后关系.方法 应用生物信息分析工具比对TCGA数据库中CCNA2基因mRNA在HCC组织和癌旁组织中表达水平;在STRING数据库中构建CCNA2蛋白-蛋白相互作用网络,并对相关蛋白功能和KEGG信号通路进行富集.根据CCNA2表达水平分为高低表达组,比较CCNA2高低组患者总生存(overall survival,OS)和无疾病进展生存(disease free survival,DFS)是否不同.回顾性分析72例手术治疗的HCC患者,采用免疫组织化学法检测患者癌组织中CCNA2蛋白表达水平与患者临床病理特征的关系,对生物信息分析结果进行验证.结果 在HCC中,CCNA2中mRNA表达水平明显高于癌旁正常肝组织;与CCNA2蛋白相互作用较为紧密的蛋白10个,蛋白间相互作用关系edge=50,区域聚类指数为0.931,与CCNA2蛋白相互作用较为紧密的10蛋白相互作用网络富集显著(P＜0.05);TOP2基因mRNA与CCNA2正向相关表达(r=0.85,P＜0.05),而CCL14基因与CCNA2负相关表达(r=-0.54,P＜0.05).CCNA2基因相关信号通路主要富集于细胞周期、病毒致癌、乙型肝炎、p53信号通路和PI3K-Akt信号通路等.预后分析提示CCNA2基因mRNA高表达患者OS(HR=1.7,P=0.0037)和DFS低于低表达组(HR=1.6,P=0.0037).免疫组化显示CCNA2蛋白在HCC患者癌组织中的高表达率为34.7％(25/72).CCNA2蛋白高表达与HCC患者肿瘤直径(P＜o.05)、DC浸润(P＜0.05)、术后2年复发/转移(P＜0.05)有关.结论 CCNA2基因在HCC患者癌组织中表达水平上调,并可作为HCC预后不良的分子标记物.
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