STAT4基因在乳腺癌中的表达意义及丹参酮ⅡA的干预

Expression and clinical significance of STAT4 in breast cancer and effects of TanshinoneⅡA on the expression of STAT4:Analysis based on the data-mining of Oncomine and GEO database

目的:整理挖掘TCGA(the Cancer Genome Atlas)和GEO(gene expression omnibus)数据库中乳腺癌基因表达数据集的相关数据,分析STAT4基因在乳腺癌中的表达及临床意义,探讨丹参酮ⅡA对乳腺癌细胞中STAT4基因的干预效果。方法:下载TCGA数据库中的乳腺癌数据集(TCGA Breast Cancer(BRCA))和GEO数据库中有关乳腺癌和丹参酮ⅡA干预乳腺癌的数据集(GSE42586、GSE85871),对所获取的数据资料进行整理并作统计分析,通过免疫印迹实验和分子对接对数据分析结果进行验证。结果:对TCGA和GEO数据库中所有关于乳腺癌和正常组织乳腺的STAT4基因表达数据进行统计分析,结果发现乳腺癌组织中STAT4基因的表达明显低于正常乳腺组织,差异有统计学意义(P<0.05)。通过生存分析发现高表达STAT4基因的乳腺癌患者无病生存期明显好于低表达者,高表达患者的预后更好(P<0.05)。GSE85871数据集中有关丹参酮ⅡA作用于乳腺癌MCF7细胞的基因表达数据表明丹参酮ⅡA可以上调MCF7细胞STAT4基因的表达水平(P<0.05),免疫印迹实验也证实经丹参酮ⅡA干预后MCF7细胞中STAT4蛋白含量增加,分子对接结果表明丹参酮ⅡA和STAT4蛋白能够形成稳定的结合构象。结论:STAT4基因在乳腺癌中表达较正常乳腺组织中偏低,且与乳腺癌患者的预后密切相关。丹参酮ⅡA能够上调MCF7细胞STAT4的基因和蛋白表达水平,该基因可能是丹参酮ⅡA干预乳腺癌的靶点之一。

OBJECTIVE To analyze the expression and clinical significance of STAT4 gene in breast cancer.by collating and mining related data of breast cancer gene experssion dataset obtained from TCGA(The Cancer Genome Atlas)and GEO(Gene Expression Omnibus)databases.Furthermore,the intervention effect of TanshinoneⅡA on STAT4 gene in breast cancer cells was explored.METHODS The Breast Cancer datasets(TCGA Breast Cancer(BRCA),GSE42586)and the TanshinoneⅡA intervention dataset(GSE85871)were downloaded from the TCGA database and GEO database,respectively.The obtained data were collated and analyzed statistically.Finally,the results of data analysis were verified by western blot experiment and molecular docking.RESULTS All the STAT4 expression data in breast cancer and normal breast tissues from TCGA and GEO databases were analyzed.It was found that the STAT4 gene expression in breast cancer tissues was significantly lower than that in normal breast tissues,with statistical significance(P<0.05).Survival analysis showed that the disease-free survival of breast cancer patients with higher STAT4 expression was significantly better than those with lower STAT4 expression,and the prognosis of patients with higher STAT4 expression was better(P<0.05).The gene expression data of MCF7 cells treated with TanshinoneⅡA in GSE85871 dataset showed that TanshinoneⅡA could increase the expression level of STAT4 gene in MCF7 cells(P<0.05).Western blot also confirmed that STAT4 protein in MCF7 cells was increased after TanshinoneⅡA intervention.Molecular docking results showed that TanshinoneⅡA and STAT4 protein could form a stable binding.CONCLUSION STAT4 gene is lower expressed in breast cancer than that in normal breast tissue,and which is closely related to the prognosis of breast cancer patients.TanshinoneⅡA can up-regulate the gene and protein expression levels of STAT4 in MCF7 cells,which may be one of the targets of TanshinoneⅡA intervention on breast cancer.