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一种三代谢基因风险评分模型可预测透明细胞肾细胞癌患者的总生存期。

A Three-Metabolic-Genes Risk Score Model Predicts Overall Survival in Clear Cell Renal Cell Carcinoma Patients.

作者信息

Zhao Yiqiao, Tao Zijia, Chen Xiaonan

机构信息

Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Front Oncol. 2020 Oct 22;10:570281. doi: 10.3389/fonc.2020.570281. eCollection 2020.

Abstract

Metabolic alterations play crucial roles in carcinogenesis, tumor progression, and prognosis in clear cell renal cell carcinoma (ccRCC). A risk score (RS) model for ccRCC consisting of disease-associated metabolic genes remains unidentified. Here, we utilized gene set enrichment analysis to analyze expression data from normal and tumor groups from the cancer genome atlas. Out of 70 KEGG metabolic pathways, we found seven and two pathways to be significantly enriched in our normal and tumor groups, respectively. We identified 113 genes enriched in these nine pathways. We further filtered 47 prognostic-related metabolic genes and used Least absolute shrinkage and selection operator (LASSO) analysis to construct a three-metabolic-genes RS model composed of , and . We further tested the RS by mapping Kaplan-Meier plots and receiver operating characteristic curves, the results were promising. Additionally, multivariate Cox analysis revealed the RS to be an independent prognostic factor. Thereafter, we considered all the independent factors and constructed a nomogram model, which manifested in better prediction capability. We validated our results using a dataset from ArrayExpress and through qRT-PCR. In summary, our study provided a metabolic gene-based RS model that can be used as a prognostic predictor for patients with ccRCC.

摘要

代谢改变在透明细胞肾细胞癌(ccRCC)的致癌作用、肿瘤进展及预后中发挥着关键作用。由疾病相关代谢基因组成的ccRCC风险评分(RS)模型仍未明确。在此,我们利用基因集富集分析来分析癌症基因组图谱中正常组和肿瘤组的表达数据。在70条KEGG代谢途径中,我们分别发现7条和2条途径在正常组和肿瘤组中显著富集。我们鉴定出9条途径中富集的113个基因。我们进一步筛选出47个与预后相关的代谢基因,并使用最小绝对收缩和选择算子(LASSO)分析构建了一个由[此处缺失基因名称]、[此处缺失基因名称]和[此处缺失基因名称]组成的三代谢基因RS模型。我们通过绘制Kaplan-Meier图和受试者工作特征曲线进一步测试了该RS,结果很有前景。此外,多变量Cox分析显示该RS是一个独立的预后因素。此后,我们综合所有独立因素构建了一个列线图模型,其表现出更好的预测能力。我们使用来自ArrayExpress的数据集并通过qRT-PCR验证了我们的结果。总之,我们的研究提供了一种基于代谢基因的RS模型,可作为ccRCC患者的预后预测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edcf/7642863/60c19c328c26/fonc-10-570281-g0001.jpg

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