HER2基因的表达水平在胶质母细胞瘤患者预后评价中的意义

Significance of the expression of HER2 gene in the prognosis evaluation of patients with glioblastoma

目的研究表明人类表皮生长因子受体2（HER2）基因的异常表达与乳腺癌,胃癌等多种恶性肿瘤的进展相关,然而其与胶质母细胞瘤（GBM）的关系目前尚不清楚。方法利用肿瘤与癌症基因图谱计划（TCGA）,脑肿瘤分子数据库（REMBRANT）和基因表达公共数据库（GEO）中GSE7696队列等中的GBM病例资料和芯片数据,通过生存分析和Cox回归分析,研究人类表皮生长因子受体2（HER2）基因的mRNA表达与GBM患者生存时间（OS）的关系。结果在TCGA病例组（N=288）中,HER2基因高表达组患者的预后差于低表达组的患者,其中位OS分别为15.1个月（95%可信区间：13.6~16.6个月）和16.7个月（95%可信区间：13.0~20.5个月）,P=0.013;同样地,在另外两个验证组的患者中,HER2基因高表达组的患者预后也差于低表达组,REMBRANT病例组的中位OS分别为12.0个月（95%可信区间：8.1~15.9个月）和17.5个月（95%可信区间：14.0~21.1个月）,P=0.002;而GSE7696病例组的中位OS则分别为11.4个月（95%可信区间：9.0~13.7个月）和15.7个月（95%可信区间：14.2~17.2个月）,P=0.044;多因素Cox回归分析表明HER2基因的表达分组不是独立的预后因素,其预后评价能力与年龄和MGMT甲基化分组因素有关。结论本研究一方面验证了HER2基因的mRNA表达与GBM患者的临床预后密切相关,另一方面为未来以HER2基因为基础的GBM预后评价方式和个体化治疗策略提供了临床依据。

Objective The dysregulation of human epidermal growth factor receptor-2（ HER2） gene is involved in various malignant tumors including breast cancers and gastric cancers.However,the relationship between HER2 gene expression and glioblastoma（ GBM） is not clear.The study aims to study the expression of HER2 gene in the evaluation of prognosis of patients with glioblastoma.Methods Genome-wide gene expression data and corresponding patient ＇s clinical data were downloaded from The Cancer Genome Atlas（ TCGA）,Repository for Molecular Brain Neoplasia Data（ REMBRANDT）,and Gene Expression Omnibus（ GEO） with accession number of GSE7696,to investigate the prognostic value of HER2 mRNA expression in GBM patients using Kaplan-Meier method and multivariate Cox regression analysis.Results In TCGA data-set（ N = 288）,patients with higher HER2 expression were associated with shorter overall survival（ OS） than patients with lower HER2 expression（ median OS：15.1 [95% confidence interval（ CI） 13.6 ~16.6]vs.16.7 [95% CI 13.0 ~20.5]months,P =0.013）; similarly,in another two validation data-sets,patients in higher expression groups had shorter OS than those in lower expression groups（ REMBRANT dataset： higher vs.lower,12.0 [95% CI 8.1 ~15.9]vs.17.5 [95% CI 14.0 ~21.1]months,P =0.002; GSE7696 dataset： higher vs.lower,11.4 [95% CI 9.0 ~13.7]vs.15.7 [95% CI 14 ~2-17.2]months,P=0.044）; HER2 mRNA expression was not an independent prognostic indictor,and its prognostic value was partly dependent on age and O（ 6）-methylguanine-DNA methyltransferase（ MGMT） promoter methylation status.Conclusion The present study indicates and validates the relationship between HER2 gene expression and GBM patients＇ OS.The study also provides the clinical evidence on HER2-based GBM subclassification and personalized medicine.