Identification and validation of an autophagy-related signature for predicting survival in lower-grade glioma.
Identification and validation of an autophagy-related signature for predicting survival in lower-grade glioma.
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DOI：
10.1080/21655979.2021.1985818
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发表时间：
2021-12
期刊：
影响因子：
4.9
通讯作者：
Pang Q
中科院分区：
文献类型：
--
作者：
Feng S;Liu H;Dong X;Du P;Guo H;Pang Q
自噬的异常水平与包括癌症在内的多种疾病的发病机制有关。然而，关于自噬相关基因（ARGs）在低级别胶质瘤（LGG）中的作用知之甚少。因此，本研究的目的是评估ARG的预后价值，并建立LGG预后的基因特征。分别从癌症基因组图谱（TCGA）和基因组组织表达数据库获得来自具有和不具有原发性LGG的患者的表达谱数据，并且使用一致聚类来鉴定具有不同疾病的患者的聚类。选择19个差异表达的ARG，阈值FDR < 0.05，|log2倍数变化（FC）|≥ 2，功能分析显示这些基因与预期的自噬过程相关。使用6个ARG的考克斯回归模型建立自噬相关特征，该模型将TCGA训练队列的患者分为高风险组和低风险组。单因素和多因素考克斯回归分析表明，基于体征的危险评分是独立的预后因素。使用TCGA测试、TCGA完整和中国胶质瘤基因组图谱队列成功验证了特征。分层分析表明，签名与临床特征和预后相关，基因集富集分析显示，自噬和癌症相关途径在高风险患者中比低风险患者中更丰富。并对6个特征相关基因的表达及预后价值进行了研究。因此，本研究构建并验证了自噬相关的预后特征，可以优化LGG患者的个体化生存预测。
Abnormal levels of autophagy have been implicated in the pathogenesis of multiple diseases, including cancer. However, little is known about the role of autophagy-related genes (ARGs) in low-grade gliomas (LGG). Accordingly, the aims of this study were to assess the prognostic values of ARGs and to establish a genetic signature for LGG prognosis. Expression profile data from patients with and without primary LGG were obtained from The Cancer Genome Atlas (TCGA) and Genome Tissue Expression databases, respectively, and consensus clustering was used to identify clusters of patients with distinct prognoses. Nineteen differentially expressed ARGs were selected with threshold values of FDR < 0.05 and |log2 fold change (FC)| ≥ 2, and functional analysis revealed that these genes were associated with autophagy processes as expected. An autophagy-related signature was established using a Cox regression model of six ARGs that separated patients from TCGA training cohort into high- and low-risk groups. Univariate and multivariate Cox regression analysis indicated that the signature-based risk score was an independent prognostic factor. The signature was successfully validated using the TCGA testing, TCGA entire, and Chinese Glioma Genome Atlas cohorts. Stratified analyses demonstrated that the signature was associated with clinical features and prognosis, and gene set enrichment analysis revealed that autophagy- and cancer-related pathways were more enriched in high-risk patients than in low-risk patients. The prognostic value and expression of the six signature-related genes were also investigated. Thus, the present study constructed and validated an autophagy-related prognostic signature that could optimize individualized survival prediction in LGG patients.
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影响因子：
11.2
作者：
Bartholomeusz C;Rosen D;Wei C;Kazansky A;Yamasaki F;Takahashi T;Itamochi H;Kondo S;Liu J;Ueno NT
通讯作者：
Ueno NT
影响因子：
13.3
作者：
Kim, Sun-Yong;Kim, Hyo Jeong;Kim, Chul-Ho
通讯作者：
Kim, Chul-Ho
影响因子：
3.9
作者：
Brigliadori, Giovanni;Foca, Flavia;Faedi, Marina
通讯作者：
Faedi, Marina
DOI：
10.1016/j.bbadis.2021.166262
发表时间：
2021-12-01
期刊：
Biochimica et biophysica acta. Molecular basis of disease
影响因子：
--
作者：
Ariosa AR;Lahiri V;Lei Y;Yang Y;Yin Z;Zhang Z;Klionsky DJ
通讯作者：
Klionsky DJ
影响因子：
64.5
作者：
Ceccarelli M;Barthel FP;Malta TM;Sabedot TS;Salama SR;Murray BA;Morozova O;Newton Y;Radenbaugh A;Pagnotta SM;Anjum S;Wang J;Manyam G;Zoppoli P;Ling S;Rao AA;Grifford M;Cherniack AD;Zhang H;Poisson L;Carlotti CG Jr;Tirapelli DP;Rao A;Mikkelsen T;Lau CC;Yung WK;Rabadan R;Huse J;Brat DJ;Lehman NL;Barnholtz-Sloan JS;Zheng S;Hess K;Rao G;Meyerson M;Beroukhim R;Cooper L;Akbani R;Wrensch M;Haussler D;Aldape KD;Laird PW;Gutmann DH;TCGA Research Network;Noushmehr H;Iavarone A;Verhaak RG
通讯作者：
Verhaak RG