基于数据库分析CK-19基因在乳腺癌中的表达及与患者预后相关性

Analysis of CK-19 gene expression in breast cancer and its correlationwith prognosis based on database mining

目的探讨肿瘤芯片数据库(Oncomine),生存分析数据库(Kaplan-Meier Plotter)和蛋白-蛋白相互作用数据库(String)平台中CK-19基因在乳腺癌中的表达及临床意义.方法分别对Oncomine、Kaplan-Meier Plotter和String进行乳腺癌CK-19基因表达情况数据挖掘.比较乳腺癌组织和对应正常组织中CK-19 mRNA表达是否存在差异.根据CK-19高低表达情况绘制生存曲线进行CK-19与乳腺癌患者预后关系分析.同时分析CK-19蛋白共表达网路,推测CK-19可能的相互作用蛋白及其生物学功能.结果检索Oncomine数据库发现,在乳腺癌中有9个数据集均显示乳腺癌中CK-19高表达.CK-19 mRNA聚类分析显示,CK-19 mRNA与KRT18,ERBB3,PRR5等基因mRNA存在共表达;在String蛋白互作数据库中对CK-19蛋白共表达进行了分析,结果显示CK-19与KRT8,KRT18等蛋白具有共表达关系.Oncomine数据库中,有3项基因表达芯片数据关于CK-19 mRNA在乳腺癌与正常组织中的差异表达分数数据,结果显示乳腺癌组织中CK-19 mR-NA表达水平高于正常乳腺组织(P<0.05).生存分析显示CK-19 mRNA高低表达组总生存期分别为90.0月和115.0月,差异比较无统计学意义(HR=1.14,95%CI:0.92~1.41,P=0.23),高低表达组无疾病进展生存期分别为48.16月和48.0个月,差异比较无统计学意义(HR=1.09,95%CI:0.98~1.22,P=0.11).应用String数据富集CK-19相互作用的可能相关蛋白,与CK-19相互作用的蛋白有10个,分别为作用评分均大于0.9,10个关联蛋白均属于细胞角蛋白家族,参与上皮细胞结构的稳定性.结论CK-19 mRNA在乳腺癌组织中高表达,其蛋白与KRT18等角蛋白家族可能共同参与了上皮细胞结构的稳定性.但CK-19 mRNA高低表达与乳腺癌患者的预后无关.

Objective To investigate the expression and clinical significance of CK-19 gene in breast cancer by data mining of Oncomine,Kaplan-Meier Plotter and String data platform.Methods Oncomine,Kaplan-Meier Plotter and String databases were used for data mining of CK-19 gene expression in breast cancer and compared the difference of CK-19 mRNA expression level between breast cancer tissue and corresponding normal breast tissues.Survival curve was drawn according to the expression of CK-19,the relationship between CK-19 mRNA expression and patients prognosis was analyzed.At the same time,the co-expression network of CK-19 protein was constructed.The possible interacting proteins relevant to CK-19 and their biological functions were also analyzed.Results After screening the Oncomine database,we found that CK-19 was overexpressed in 9 breast cancer datasets.Cluster analysis of CK-19 mRNA showed that CK-19 was co-expressed with KRT18,ERBB3 and PRR5.The co-expression of CK-19 in String protein database was analyzed and demonstrated that CK-19 was co-expressed with KRT8,KRT18 and other proteins.In Oncomine database,there are three gene expression chip data about the differential expression of CK-19 in breast cancer and normal tissue.The results showed that the expression level of CK-19 mRNA in breast cancer tissue was significantly higher than that in normal breast tissue(P<0.05).Survival analysis showed that the overall survival of CK-19 high and low expression groups were 90.10 months and 115.10 months,respectively,without significant difference(HR=1.14,95%CI:0.92—1.41,P=0.23).The progression-free survival of CK-19 high and low expression groups were 48.16 months and 48.0 months,respectively,with no significant difference(HR=1.09,95%CI:0.98—1.22,P=0.11).Proteins network relevant to CK-19 was enriched by String database.There were 10 proteins interacting with CK-19,with action scores greater than 0.9,respectively.The 10 associated proteins were related to the cytokeratin family and participated in the structural stability of epithelial cells.Conclusion CK-19 is highly expressed in breast cancer tissues,its protein and KRT18 family may be involved in the stability of epithelial cell structure.However,the expression of CK-19 is not related to the prognosis of breast cancer patients.