Jin Shuai, Qian Zenghui, Liang Tingyu, Liang Jingshan, Yang Fuqiang, Sun Lihua, Li Wenbin, Qiu Xiaoguang, Zhang Man
Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China; The General Hospital of Chinese People's Armed Police Forces, Beijing, China.
Beijing Neurosurgical Institute, Capital Medical University, Beijing, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
World Neurosurg. 2018 Sep;117:e34-e41. doi: 10.1016/j.wneu.2018.05.122. Epub 2018 May 26.
Glioblastoma (GBM) is an extremely challenging malignancy to treat. Although temozolomide (TMZ) is a standard treatment regimen, many patients with GBM develop chemoresistance. The aim of this study was to identify a DNA repair-related gene signature to better stratify patients treated with TMZ.
We selected 89 cases of primary GBM (pGBM) from the Chinese Glioma Genome Atlas RNA-seq dataset as the training cohort, whereas The Cancer Genome Atlas RNA-seq and Gene Set Enrichment (GSE) 16011 mRNA array sets were used as validation cohorts. Regression analysis and linear risk score assessment were performed to build a DNA repair-related signature. We used Kaplan-Meier analysis to evaluate the predictive value of the signature for overall survival (OS) in the different groups. Multivariate Cox regression analysis was used to determine whether the 5-gene signature could independently predict OS.
Using our 5-gene signature panel of APEX1, APRT, PARP2, PMS2L2, and POLR2L, we divided patients with pGBM into high- and low-risk groups. Patients with a low-risk score were predicted to have favorable survival and greater benefit from TMZ therapy compared with patients from the high-risk group (P < 0.05). Moreover, receiver operating characteristic curves showed that the multigene signature was the most sensitive and specific model for survival prediction (P < 0.05).
Among patients with pGBM, classification based on a risk score determined using a 5-gene panel indicated different OS and reaction to TMZ. The findings in this study demonstrate that this unique 5-gene signature could be a novel model to predict OS and provide accurate therapy for patients with pGBM.
胶质母细胞瘤（GBM）是一种治疗极具挑战性的恶性肿瘤。尽管替莫唑胺（TMZ）是标准治疗方案，但许多GBM患者会产生化疗耐药性。本研究的目的是识别一种与DNA修复相关的基因特征，以便更好地对接受TMZ治疗的患者进行分层。
我们从中国胶质瘤基因组图谱RNA测序数据集中选取89例原发性GBM（pGBM）病例作为训练队列，而癌症基因组图谱RNA测序和基因集富集（GSE）16011 mRNA阵列集用作验证队列。进行回归分析和线性风险评分评估以构建与DNA修复相关的特征。我们使用Kaplan-Meier分析来评估该特征对不同组总生存期（OS）的预测价值。多变量Cox回归分析用于确定5基因特征是否可以独立预测OS。
使用我们的APEX1、APRT、PARP2、PMS2L2和POLR2L的5基因特征面板，我们将pGBM患者分为高风险和低风险组。与高风险组患者相比，低风险评分的患者预计生存期更佳且从TMZ治疗中获益更大（P < 0.05）。此外，受试者工作特征曲线表明，多基因特征是生存预测最敏感和特异的模型（P < 0.05）。
在pGBM患者中，基于使用5基因面板确定的风险评分进行分类表明OS和对TMZ的反应不同。本研究结果表明，这种独特的5基因特征可能是预测OS的新模型，并为pGBM患者提供准确的治疗。
