【摘要】 目的 筛选宫颈癌组织中差异表达的基因,分析其与宫颈癌预后间的关系,得出其作为宫颈癌预后评估新标志物的可能性。方法 从GEO数据库获取宫颈癌和正常宫颈组织的转录组测序结果的数据。通过在线GEO2R工具分析得到宫颈癌和正常宫颈组织中的差异表达基因。用“仙桃学术”进行GO和KEGG分析。基于String网站和Cytoscape软件构建蛋白-蛋白相互作用(PPI)网络并筛选出枢纽基因。通过Kaplan-Meier和Cox单因素回归分析枢纽基因对患者总生存期(OS)和无复发生存期(RFS)的影响及与其临床特征的关联。通过在线数据库GEPIA database,the Human Protein Atlas和临床样本进行枢纽基因表达的验证。采用受试者工作特征(ROC)曲线来评估枢纽基因表达水平对区分宫颈癌组织和正常宫颈组织的可行性。结果 在公共数据集中得到79个差异表达基因,有30个基因表达上调,49个基因表达下调。富集分析显示,AURKA基因主要参与“细胞周期”、“孕酮介导的卵细胞成熟”和“铂耐药性”等通路。蛋白质相互作用网络及枢纽基因生存分析得出AURKA基因的高表达与宫颈癌患者总生存期及无复发生存期较短显著相关(P<0.05)。通过数据库及临床样本进一步验证得出AURKA基因的mRNA和蛋白在宫颈癌中表达显著上调且无种族人群差异。ROC结果显示曲线下面积(AUC)为0.999,表明AURKA基因表达水平对宫颈癌具有较高的预测价值。结论 宫颈癌组织中AURKA mRNA和蛋白表达上调,则宫颈癌患者的总生存期和无复发生存期均缩短,AURKA基因具有作为宫颈癌预后评估标志物及靶点的潜在可能。更多还原

【Abstract】 Objective To explore the relationship between the expression of AURKA in cervical carcinoma tissues and the prognosis of cervical carcinoma and find out the potential of new cervical carcinoma marker for prognosis assessment. Methods The transcriptome sequencing data of cervical carcinoma and normal cervical tissues were obtained from the GEO database. Differentially expressed genes in cervical carcinoma and normal cervical tissues were analyzed by GEO2R online. GO and KEGG analysis were performed by“Xiantao Academic”. Construct protein-protein interaction(PPI)network and screen out Hub genes based on String website and Cytoscape software. The effects of hub genes on overall survival(OS)and recurrence-free survival(RFS)and their association with their clinical characteristics were analyzed by Kaplan-Meier and Cox univariate regression. Validation of hub gene expression was performed through the online database GEPIA database,the Human Protein Atlas and clinical samples. The receiver operating characteristic(ROC)curves were used to assess the feasibility of hub gene expression levels to distinguish cervical carcinoma tissues and normal cervical tissues. Results Among the 79 differentially expressed genes in the public datasets,30 genes were upregulated and 49 genes were downregulated. Enrichment analysis revealed that the AURKA gene was mainly involved in pathways such as“cell cycle”,“progesterone-mediated egg maturation”and“platinum resistance”. Protein interaction network and hub gene survival analysis showed that high expression of AURKA gene was significantly associated with shorter overall survival and recurrence-free survival of cervical carcinoma patients(P<0.05).Further validation by database and clinical samples showed that the mRNA and protein expression of AURKA gene were significantly upregulated in cervical carcinoma and there was no ethnic population difference. The ROC result showed the area under the curve(AUC)was 0.999,indicating that the AURKA gene expression level has a high predictive value for cervical carcinoma. Conclusion The expression of AURKA mRNA and protein is upregulated in cervical carcinoma tissues,which can shorten the overall survival rate and disease-free survival of patients with cervical carcinoma. AURKA gene may be a prognostic marker for cervical carcinoma.更多还原