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

SU Hui; DAI Yiwu; QIN Jiazhen; BAI Miaochun; YANG Yi; XU Ruxiang

Abstract：Objective The dysregulation of human epidermal growth factor receptor-2 ( HER2 ) gene is involved in various malignant tumors including breast cancers and gastric cancers. Howeve,r 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 HER 2 gene expression and GBM patients'OS.The study also provides the clinical evidence on HER 2-based GBM subclassification and personalized medicine.