基于生物信息学分析RSK1在乳腺癌中的表达及其预后预测价值

Analysis of RSK1 expression in breast cancer and its prognostic value based on bioinformatics method

目的探讨核糖体S6蛋白激酶1(ribosomal S6 protein kinase type 1,RSK1)在乳腺癌中的表达及其预后预测价值。方法基于Protein Atlas数据库比较乳腺癌组织及正常乳腺组织中RSK1表达差异。基于TCGA-BRCA及GEO提取RSK1 mRNA表达数据,基于TCGA-RPPA提取RSK1蛋白表达数据,分析RSK1 mRNA及蛋白表达水平及其与乳腺癌总体预后的关系。结果数据集免疫组化分析结果显示,乳腺癌组织RSK1蛋白表达水平较正常组织低。TCGA-BRCA数据单因素和多因素Cox回归分析均显示RSK1 mRNA高表达组患者总体预后较好,分层分析结果显示女性、年龄≤60岁、Ⅰ~Ⅱ期、浸润性乳腺癌、无区域淋巴结转移(N0)以及无远处转移(M0)的高表达RSK1 mRNA患者总体预后较好。GEO 9个基于基因芯片数据集的荟萃结果与其相一致(HR=0.69,95%CI:0.56~0.86,P=0.002)。TCGA-RPPA数据显示RSK1蛋白高表达组患者总体预后较好(HR=0.49,95%CI:0.27~0.89,P=0.011),不同乳腺癌分期中,早期患者RSK1 mRNA(HR=0.61,95%CI:0.39~0.95,P=0.025)和蛋白(HR=0.43,95%CI:0.22~0.84,P=0.008)高表达组总体预后较好。结论RSK1高表达与乳腺癌患者较好的总体预后相关,RSK1可能是预测乳腺癌患者总体预后的标志物。

Objective To investigate the expression of ribosomal S6 protein kinase type 1(RSK1)in breast cancer and its prognostic value.Methods The RSK1 expressions in breast cancer tissues and normal breast tissues were compared based on the Protein Atlas database.The RSK1 mRNA expression data were extracted from TCGA-BRCA and GEO database,the RSK1 protein expression data were obtained from TCGA-RPPA database,to analyze the RSK1 mRNA and protein expression and its relationship with the overall prognosis of breast cancer.Results The immunohistochemical analysis of the dataset showed that the expression level of RSK1 protein in breast cancer tissues was lower than that in normal tissues.The univariable and multivariable Cox regression analysis of TCGA-BRCA database showed that the patients with high level of RSK1 mRNA had a better prognosis.The results of stratified analysis showed that female patients,age≤60 years,StageⅠ-Ⅱ,infiltrating carcinoma,no regional lymph node metastasis(N0),and no distant metastasis(M0)with high expression of RSK1 mRNA had a better prognosis.The meta-analysis results of 9 microarray datasets of GEO database was consistent with the TCGA-BRCA database(HR=0.69,95%CI:0.56-0.86,P=0.002).The TCGA-RPPA data showed that the patients with high RSK1 protein level had a better prognosis(HR=0.49,95%CI:0.27-0.89,P=0.011),and the patients in different stages of breast cancer with high expression of RSK1 mRNA and protein were associated with better prognosis(HR=0.61,95%CI:0.39-0.95,P=0.025;HR=0.43,95%CI:0.22-0.84,P=0.008).Conclusions High expression of RSK1 is associated with a better overall prognosis of breast cancer patients,and RSK1 can be a biomarker to predict the overall prognosis for breast cancer,especially for patients at early stage.