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基于 6 个代谢相关基因特征的透明细胞肾细胞癌临床预后的更好预测。

Better prediction of clinical outcome in clear cell renal cell carcinoma based on a 6 metabolism-related gene signature.

机构信息

Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.

Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

Sci Rep. 2023 Jul 17;13(1):11490. doi: 10.1038/s41598-023-38380-7.

Abstract

It has been reported that metabolic disorders participate in the formation and progression of clear cell renal cell carcinoma (ccRCC). However, the predictive value of metabolism-related genes (MRGs) in clinical outcome of ccRCC is still largely unknown. Herein, a novel metabolism-related signature was generated to assess the effect of MRGs on the prognosis of ccRCC patients. Important module MRGs were selected by differentially expressed analysis and WGCNA. Subsequently, the hub MRGs were screened via univariate cox regression as well as LASSO regression. A new metabolism-related signature of 6 hub MRGs (PAFAH2, ACADSB, ACADM, HADH, PYCR1 and ITPKA) was constructed, with a good prognostic prediction ability in the TCGA cohort. The prediction accuracy of this signature was further confirmed in both GSE22541 and FAHWMU cohort. Interestingly, this MRG risk signature was highly correlated with tumor mutation burden and immune infiltration in ccRCC. Notably, lower PAFAH2, a member of 6 MRGs, was found in ccRCC. Knockdown of PAFAH2 contributed to renal cancer cell proliferation and migration. Collectively, a 6-MRG prognostic risk signature is generated to estimate the prognostic status of ccRCC patients, providing a novel insight in the prognosis prediction and treatment of ccRCC.

摘要

据报道,代谢紊乱参与了透明细胞肾细胞癌(ccRCC)的形成和进展。然而,代谢相关基因(MRGs)在 ccRCC 临床结局中的预测价值在很大程度上仍然未知。在此,生成了一个新的代谢相关特征,以评估 MRGs 对 ccRCC 患者预后的影响。通过差异表达分析和 WGCNA 选择重要的模块 MRGs。随后,通过单变量 cox 回归和 LASSO 回归筛选出关键的 MRGs。构建了一个由 6 个关键 MRGs(PAFAH2、ACADSB、ACADM、HADH、PYCR1 和 ITPKA)组成的新的代谢相关特征,在 TCGA 队列中具有良好的预后预测能力。该特征的预测准确性在 GSE22541 和 FAHWMU 队列中也得到了进一步的证实。有趣的是,这个 MRG 风险特征与 ccRCC 中的肿瘤突变负担和免疫浸润高度相关。值得注意的是,在 ccRCC 中发现了 6 个 MRGs 中的一个成员 PAFAH2 表达水平较低。PAFAH2 的敲低促进了肾癌细胞的增殖和迁移。总之,生成了一个 6-MRG 预后风险特征,以估计 ccRCC 患者的预后状态,为 ccRCC 的预后预测和治疗提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3eb6/10352344/151d2f5b2b63/41598_2023_38380_Fig1_HTML.jpg

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