A three-gene signature for prognosis in patients with MGMT promoter-methylated glioblastoma
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Wen Wang1,2,3,7, Lu Zhang5, Zheng Wang2,3,7, Fan Yang2,3,7, Haoyuan Wang6,7, Tingyu Liang2,3,7, Fan Wu3,4,7, Qing Lan1, Jiangfei Wang2,4,7, Jizong Zhao2,1,8
1Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, China
2Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
3Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
4Brain Tumor Center, Beijing Institute for Brain Disorders, Beijing, China
5Department of Ophthalmology, School of Medicine, Shandong University, Jinan, China
6Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
7Chinese Glioma Cooperative Group (CGCG), Beijing, China
8China National Clinical Research Center for Neurological Diseases, Beijing, China
Jizong Zhao, email: [email protected]
Keywords: signature, MGMT, prognosis, glioblastoma, RNA-Seq
Received: February 27, 2016 Accepted: August 09, 2016 Published: August 31, 2016
Glioblastoma is the most malignant tumor and has high mortality rate. The methylated prompter of MGMT results in chemotherapy sensitivity for these patients. However, there are still other factors that affected the prognosis for the glioblastoma patients with similar MGMT methylation status. We developed a signature with three genes screened from the whole genome mRNA expression profile from Chinese Glioma Genome Atlas (CGGA) and RNAseq data from The Cancer Genome Atlas (TCGA). Patients with MGMT methylation in low risk group had longer survival than those in high risk group (median overall survival 1074 vs. 372 days; P = 0.0033). Moreover, the prognostic value of the signature was significant difference in cohorts stratified by MGMT methylation and chemotherapy (P=0.0473), while there is no significant difference between low and high risk group or unmethylated MGMT patients without chemotherapy. Multivariate analysis indicated that the risk score was an independent prognosis factor (P = 0.004). In conclusion, our results showed that the signature has prognostic value for patients with MGMT promoter-methylated glioblastomas based on bioinformatics analysis.
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