A Novel Cuproptosis-Related Prognostic Gene Signature and Validation of Differential Expression in Clear Cell Renal Cell Carcinoma

被引:224
作者
Bian, Zilong [1 ]
Fan, Rong [1 ]
Xie, Lingmin [2 ]
机构
[1] Zhejiang Univ, Sch Med, Sch Publ Hlth, Dept Big Data Hlth Sci, Hangzhou 310058, Peoples R China
[2] Zhejiang Univ, Sch Med, Affiliated Sir Run Run Shaw Hosp, Dept Surg Oncol, Hangzhou 310016, Peoples R China
关键词
cuproptosis; ccRCC; overall survival; progression-free survival; cell death; PROGRESSION-FREE SURVIVAL; DEATH; INHIBITION; POINT;
D O I
10.3390/genes13050851
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cell carcinoma, which is characterized by metabolic reprogramming. Cuproptosis, a novel form of cell death, is highly linked to mitochondrial metabolism and mediated by protein lipoylation. However, the clinical impacts of cuproptosis-related genes (CRGs) in ccRCC largely remain unclear. In the current study, we systematically evaluated the genetic alterations of cuproptosis-related genes in ccRCC. Our results revealed that CDKN2A, DLAT, DLD, FDX1, GLS, PDHA1 and PDHB exhibited differential expression between ccRCC and normal tissues (|log(2)(fold change)| > 2/3 and p < 0.05). Utilizing an iterative sure independence screening (SIS) method, we separately constructed the prognostic signature of CRGs for predicting the overall survival (OS) and progression-free survival (PFS) in ccRCC patients. The prognostic score of CRGs yielded an area under the curve (AUC) of 0.658 and 0.682 for the prediction of 5-year OS and PFS, respectively. In the Kaplan-Meier survival analysis of OS, a higher risk score of cuproptosis-related gene signature was significantly correlated with worse overall survival (HR = 2.72 (2.01-3.68), log-rank p = 1.76 x 10(-7)). Patients with a higher risk had a significantly shorter PFS (HR = 2.83 (2.08-3.85), log-rank p = 3.66 x 10(-7)). Two independent validation datasets (GSE40435 (N = 101), GSE53757 (N = 72)) were collected for meta-analysis, suggesting that CDKN2A (log(2)(fold change) = 1.46, 95%CI: 1.75-2.35) showed significantly higher expression in ccRCC tissues while DLAT (log(2)(fold change) = -0.54, 95%CI: -0.93--0.15) and FDX1 (log(2)(fold change) = -1.01, 95%CI: -1.61--0.42) were lowly expressed. The expression of CDKN2A and FDX1 in ccRCC was also significantly associated with immune infiltration levels and programmed cell death protein 1 (PD-1) expression (CDKN2A: r = 0.24, p = 2.14 x 10(-8); FDX1: r = -0.17, p = 1.37 x 10(-4)). In conclusion, the cuproptosis-related gene signature could serve as a potential prognostic predictor for ccRCC patients and may offer novel insights into the cancer treatment.
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页数:16
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