The evaluation of the prognosis of glioblastoma patients by methylation state risk analysis

KANG Enming; ZHANG Wei; ZHANG Xiang

Abstract：Objective The changes of methylation status within cytosine-phosphate-guanine (CpG) island shores (GCI shores) occurred more frequently than CpG islands (CGI) in gliblastoma multiforme (GBM).However,the relationship between methylation pattens of GCI shores and GBM was not clear.Methods Genome-wide gene methylation data and corresponding patient's clinical data were downloaded from The Cancer Genome Atlas (TCGA),Gene Expression Omnibus (GEO) with accession number of GSE36278 and GSE20274.The prognostic value of 7-GCI methylation signature in GBM patients was investigated by Kaplan-Meier method and multivariate Cox regression analysis.Results In TCGA dataset (n =136),patients in high risk group had shorter overall survival (OS) than patients in low risk group [median OS:8.1 [95％ confidence interval (CI):5.8 ～ 10.5] vs 20.1 (95％ CI:17.4 ～22.8) months,P＜0.001];in GSE36278 dataset (n =37),patients in high risk group had shorter overall survival (OS) than patients in low risk group [median OS:12 (95％ CI:11.5 ～12.5) vs 15 (95％ CI:12.4 ～17.6) months,P =0.023];in validation dataset GSE60274 (n =62),patients in high risk group had shorter overall survival (OS)than patients in low risk group [median OS:10.5 (95％ CI:7.8～13.1) vs 16 (95％ CI:14.3 ～17.7) months,P=0.003].Multivariate Cox regression analysis showed 7-GCI signature to be a prognosticator independent of age and O (6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status.Conclusion The present study identifies and validates a prognostic risk score formula based on 7 GCI shores methylation status.