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构建并验证一个用于预测结肠癌预后的代谢风险模型。

Construction and validation of a metabolic risk model predicting prognosis of colon cancer.

机构信息

Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin Province, China.

Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun, Jilin, China.

出版信息

Sci Rep. 2021 Mar 25;11(1):6837. doi: 10.1038/s41598-021-86286-z.

Abstract

Metabolic genes have played a significant role in tumor development and prognosis. In this study, we constructed a metabolic risk model to predict the prognosis of colon cancer based on The Cancer Genome Atlas (TCGA) and validated the model by Gene Expression Omnibus (GEO). We extracted 753 metabolic genes and identified 139 differentially expressed genes (DEGs) from TCGA database. Then we conducted univariate cox regression analysis and Least Absolute Shrinkage and Selection Operator Cox regression analysis to identify prognosis-related genes and construct the metabolic risk model. An eleven-gene prognostic model was constructed after 1000 resamples. The gene signature has been proved to have an excellent ability to predict prognosis by Kaplan-Meier analysis, time-dependent receiver operating characteristic, risk score, univariate and multivariate cox regression analysis based on TCGA. Then we validated the model by Kaplan-Meier analysis and risk score based on GEO database. Finally, we performed a weighted gene co-expression network analysis and protein-protein interaction network on DEGs, and Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology enrichment analyses were conducted. The results of functional analyses showed that most significantly enriched pathways focused on metabolism, especially glucose and lipid metabolism pathways.

摘要

代谢基因在肿瘤的发生和预后中起着重要作用。本研究基于癌症基因组图谱(TCGA)构建了一个代谢风险模型,以预测结肠癌的预后,并通过基因表达综合数据库(GEO)进行了验证。我们从 TCGA 数据库中提取了 753 个代谢基因,并鉴定了 139 个差异表达基因(DEGs)。然后,我们进行了单变量 cox 回归分析和最小绝对值收缩和选择算子 cox 回归分析,以鉴定与预后相关的基因,并构建代谢风险模型。经过 1000 次重采样后,构建了一个由 11 个基因组成的预后模型。基于 TCGA 的 Kaplan-Meier 分析、时间依赖性接受者操作特征、风险评分、单变量和多变量 cox 回归分析证明了基因特征具有良好的预后预测能力。然后,我们通过 GEO 数据库的 Kaplan-Meier 分析和风险评分验证了该模型。最后,我们对 DEGs 进行了加权基因共表达网络分析和蛋白质-蛋白质相互作用网络分析,并进行了京都基因与基因组百科全书通路和基因本体论富集分析。功能分析的结果表明,大多数显著富集的通路集中在代谢方面,特别是葡萄糖和脂质代谢通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3da4/7994414/8d68da3976ea/41598_2021_86286_Fig1_HTML.jpg

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