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自噬相关五基因特征对低级别胶质瘤患者的预后价值

Prognostic Value of an Autophagy-Related Five-Gene Signature for Lower-Grade Glioma Patients.

作者信息

Guo Jin-Cheng, Wei Qing-Shuang, Dong Lei, Fang Shuang-Sang, Li Feng, Zhao Yi

机构信息

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

出版信息

Front Oncol. 2021 Mar 9;11:644443. doi: 10.3389/fonc.2021.644443. eCollection 2021.

Abstract

Molecular characteristics can be good indicators of tumor prognosis and have been introduced into the classification of gliomas. The prognosis of patients with newly classified lower-grade gliomas (LGGs, including grade 2 and grade 3 gliomas) is highly heterogeneous, and new molecular markers are urgently needed. Autophagy related genes (ATGs) were obtained from Human Autophagy Database (HADb). From the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), gene expression profiles including ATG expression information and patient clinical data were downloaded. Cox regression analysis, receiver operating characteristic (ROC) analysis, Kaplan-Meier analysis, random survival forest algorithm (RSFVH) and stratification analysis were performed. Through univariate Cox regression analysis, we found a total of 127 ATGs associated with the prognosis of LGG patients from TCGA dataset and a total of 131 survival-related ATGs from CGGA dataset. Using TCGA dataset as the training group ( = 524), we constructed a five-ATG signature (including BAG1, BID, MAP1LC3C, NRG3, PTK6), which could divide LGG patients into two risk groups with significantly different overall survival (Log Rank < 0.001). Then we confirmed in the independent CGGA dataset that the five-ATG signature had the ability to predict prognosis ( = 431, Log Rank < 0.001). We further discovered that the predictive ability of the five-ATG signature was better than the existing clinical indicators and IDH mutation status. In addition, the five-ATG signature could further classify patients after receiving radiotherapy or chemotherapy into groups with different prognosis. We identified a five-ATG signature that could be a reliable prognostic marker and might be therapeutic targets for autophagy therapy for LGG patients.

摘要

分子特征可以作为肿瘤预后的良好指标,并已被引入胶质瘤的分类中。新分类的低级别胶质瘤(LGG,包括2级和3级胶质瘤)患者的预后高度异质,迫切需要新的分子标志物。自噬相关基因(ATG)从人类自噬数据库(HADb)中获取。从癌症基因组图谱(TCGA)和中国胶质瘤基因组图谱(CGGA)下载了包括ATG表达信息和患者临床数据的基因表达谱。进行了Cox回归分析、受试者工作特征(ROC)分析、Kaplan-Meier分析、随机生存森林算法(RSFVH)和分层分析。通过单变量Cox回归分析,我们从TCGA数据集中发现了总共127个与LGG患者预后相关的ATG,从CGGA数据集中发现了总共131个与生存相关的ATG。以TCGA数据集作为训练组(n = 524),我们构建了一个包含五个ATG的特征(包括BAG1、BID、MAP1LC3C、NRG3、PTK6),该特征可以将LGG患者分为两个总生存期有显著差异的风险组(对数秩检验 < 0.001)。然后我们在独立的CGGA数据集中证实,这个包含五个ATG的特征具有预测预后的能力(n = 431,对数秩检验 < 0.001)。我们进一步发现,这个包含五个ATG的特征的预测能力优于现有的临床指标和IDH突变状态。此外,这个包含五个ATG的特征可以在接受放疗或化疗后进一步将患者分为不同预后的组。我们确定了一个包含五个ATG的特征,它可能是一个可靠的预后标志物,并且可能是LGG患者自噬治疗的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6932/7985555/1ed66c0188a0/fonc-11-644443-g0001.jpg

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