Identification of SEC61G as a Novel Prognostic Marker for Predicting Survival and Response to Therapies in Patients with Glioblastoma
Identification of SEC61G as a Novel Prognostic Marker for Predicting Survival and Response to Therapies in Patients with Glioblastoma
复制标题
鉴定 SEC61G 作为预测胶质母细胞瘤患者生存和治疗反应的新型预后标志物
DOI：
10.12659/msm.916648
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发表时间：
2019-05-16
影响因子：
3.1
通讯作者：
Cheng, Quan
中科院分区：
文献类型：
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作者：
Liu, Bo;Liu, Jingping;Cheng, Quan
背景胶质母细胞瘤（GBM）患者的生存率和治疗结果差异很大。治疗抵抗，包括对替莫唑胺（TMZ）和放射治疗的抵抗，是这些治疗的一个很大障碍。在这项研究中，我们的目的是评估SEC 61 G对GBM患者生存和治疗反应的预测价值。材料/方法生存分析用于评估来自癌症基因组图谱（TCGA）和中国胶质瘤基因组图谱（CGGA）数据集的GBM患者的SEC 61 G表达与生存之间的相关性。采用单因素和多因素考克斯比例风险回归分析确定具有独立影响力的预后因素。基因集富集分析（GSEA）和基因集变异分析（GSVA）进行了说明SEC 61 G可能的生物学功能。结果GBM中SEC 61 G高表达与预后不良相关。SEC 61 G的高表达也与TCGA GBM队列中接受TMZ治疗或放疗的患者的不良结局相关。单因素和多因素考克斯比例风险回归分析表明，SEC 61 G是影响预后和治疗结果的独立预后因素。在生存分析中，年龄、SEC 61 G表达和MGMT启动子甲基化的组合可以提供更好的结果评估。最后，在GSEA和GSVA中观察到SEC 61 G表达与Notch通路之间的强相关性，这提示SEC 61 G影响存活和TMZ抗性的可能机制。结论SEC 61 G表达可能是GBM患者生存不良的潜在预后指标，也可能是TMZ治疗和放射治疗预后不良的预测因子。
Background The survival and therapeutic outcome vary greatly among glioblastoma (GBM) patients. Treatment resistance, including resistance to temozolomide (TMZ) and radiotherapy, is a great obstacle for these therapies. In this study, we aimed to evaluate the predictive value of SEC61G on survival and therapeutic response in GBM patients. Material/Methods Survival analyses were performed to assess the correlation between SEC61G expression and survival of GBM patients from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) datasets. Univariate and multivariate Cox proportional hazard regression analysis was introduced to determine prognostic factors with independent impact power. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were conducted to illustrate possible biological functions of SEC61G. Results High expression of SEC61G was significantly correlated with poor prognosis in all GBM patients. High expression of SEC61G was also associated with poor outcome in those who received TMZ treatment or radiotherapy in TCGA GBM cohort. Univariate and multivariate Cox proportional hazards regression demonstrated that SEC61G was an independent prognostic factor affecting the prognosis and therapeutic outcome. The combination of age, SEC61G expression, and MGMT promoter methylation in survival analysis could provide better outcome assessment. Finally, a strong correlation between SEC61G expression and Notch pathway was observed in GSEA and GSVA, which suggested a possible mechanism that SEC61G affected survival and TMZ resistance. Conclusions SEC61G expression may be a potential prognostic marker of poor survival, and a predictor of poor outcome to TMZ treatment and radiotherapy in GBM patients.