Development and validation of a nomogram with an autophgy-related gene signature for predicting survival in patients with glioblastoma

被引:82
作者
Wang, Zihao [1 ,2 ]
Gao, Lu [1 ,2 ]
Guo, Xiaopeng [1 ,2 ]
Feng, Chenzhe [1 ,2 ]
Lian, Wei [1 ,2 ]
Deng, Kan [1 ,2 ]
Xing, Bing [1 ,2 ]
机构
[1] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Neurosurg, Beijing 100730, Peoples R China
[2] Chinese Pituitary Adenoma Cooperat Grp, China Pituitary Dis Registry Ctr, Beijing 100730, Peoples R China
来源
AGING-US | 2019年 / 11卷 / 24期
关键词
glioblastoma; GSEA; autophagy; gene signature; prognostic model; EXPRESSION; GLIOMA; CANCER; CLASSIFICATION; MULTIFORME; MUTATIONS; MIGRATION; MODELS; TREE;
D O I
10.18632/aging.102566
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Glioblastoma (GBM) is the most common brain tumor with significant morbidity and mortality. Autophagy plays a vital role in GBM development and progression. We aimed to establish an autophagy-related multigene expression signature for individualized prognosis prediction in patients with GBM. Differentially expressed autophagy-related genes (DE-ATGs) in GBM and normal samples were screened using TCGA. Univariate and multivariate Cox regression analyses were performed on DE-ATGs to identify the optimal prognosis-related genes. Consequently, NRG1 (HR=1.142, P=0.008), ITGA3 (HR=1.149, P=0.043), and MAP1LC3A (HR=1.308, P=0.014) were selected to establish the prognostic risk score model and validated in the CGGA validation cohort. GSEA revealed that these genes were mainly enriched in cancer- and autophagy-related KEGG pathways. Kaplan-Meier survival analysis demonstrated that patients with high risk scores had significantly poorer overall survival (OS, log-rank P= 6.955x10(-5)). The autophagy signature was identified as an independent prognostic factor. Finally, a prognostic nomogram including the autophagy signature, age, pharmacotherapy, radiotherapy, and IDH mutation status was constructed, and TCGA/CGGA-based calibration plots indicated its excellent predictive performance. The autophagy-related three-gene risk score model could be a prognostic biomarker and suggest therapeutic targets for GBM. The prognostic nomogram could assist individualized survival prediction and improve treatment strategies.
引用
收藏
页码:12246 / 12269
页数:24
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