BRIP1在胶质瘤中的表达及临床意义

目的 探讨乳腺癌易感基因相互作用蛋白1（BRIP1）在胶质瘤中的表达及其与病人预后的相关性。方法 从GEO数据库GPL570平台选取三个BRIP1基因表达谱芯片（GSE4290、GSE50161和GSE74195）分析胶质瘤BRIP1的表达情况。使用TCGA下载有关胶质瘤BRIP1表达、生存率和临床特征的数据，多因素Cox比例回归风险模型分析胶质瘤生存预后的影响因素；利用受试者工作特征（ROC）曲线评估BRIP1表达水平与胶质瘤生存预后的关系；通过基因富集分析胶质瘤BRIP1相关的细胞信号通路。结果 胶质瘤BRIP1表达水平相比于正常样本明显升高（P<0.05）。多因素Cox回归分析结果表明，BRIP1高表达（HR=1.250；95% CI: 1.056~1.480；P<0.001）是胶质瘤不良预后的独立危险因素。生存曲线分析显示，相较于BRIP1低表达组，BRIP1高表达组胶质瘤生存期明显缩短（P<0.001）。ROC曲线分析显示BRIP1表达水平预测胶质瘤1年不良预后的曲线下面积（AUC）为0.744，最佳截断值为0.302，敏感性为0.832，特异性为0.528；预测3年不良预后的AUC为0.801，最佳截断值为0.420，敏感性为0.696，特异性为0.809；预测5年不良预后的AUC为0.767，最佳截断值为0.420时，敏感性为0.593，特异性为0.842。基因富集分析显示BRIP1基因主要富集于DNA复制、同源重组、错配修复和细胞周期等信号转导通路。结论 BRIP1在人脑胶质瘤表达上调，与胶质瘤不良预后密切相关。

Expression of BRIP1 in human glioma tissues and its clinical significance based on bioinformatic analysis

Objective To investigate the expression change of BRCA interacting protein C-terminal helicase 1 (BRIP1) in human glioma tissues and its clinical meanings. Methods The chip datasets of GSE4290, GSE50161 and GSE74195 were downloaded from the GEO to analyze the expression of BRIP1 in human giloma tissues. The TCGA database was used to search for the date ofBRIP1 expression in clinical samples. Multivariate Cox proportional risk regression model was used to analyze the independent prognostic indicators of glioma patients. ROC curve was used to analyze the relationship of BRIP1 expression and survival prognosis of glioma patients. GSEA was used to predict the molecular pathways related to BRIP1 in the glioma tissues. Results The BRIP1 expression level in glioma tissues was significantly increased compared to the normal sample (P<0.05). Multivariate Cox regression analysis showed that high expression of BRIP1 was an independent risk factor for poor prognosis of glioma patients (HR=1.056; 95% CI 1.056~1.480; P<0.001). The survival curve analysis showed that the survival time of BRIP1 high expression group was significantly shortened compared to the BRIP1 low expression group (P<0.001). ROC curve analysis showed that the area under curve (AUC) of BRIP1 expression level for predicting 1-year poor prognosis of glioma patients was 0.744, the cut-off value was 0.302, the sensitivity was 0.832, and the specificity was 0.528; For prdicting 3-year poor prognosis, the AUC was 0.801, the cut-off value was 0.420, the sensitivity was 0.696, and the specificity was 0.809; For predicting 5-year poor prognosis, the AUC was 0.767, the cut-off value was 0.420, the sensitivity was 0.593, and the specificity was 0.842. Gene enrichment analysis showed that the BRIP1 gene was mainly enriched in signal transduction pathways such as DNA replication, homologous recombination, mismatch repair and cell cycle. Conclusions BRIP1 is up-regulated in human glioma tissues, which is associated with the poor prognosis of glioma patients.