Integrated Analysis to Identify a Redox-Related Prognostic Signature for Clear Cell Renal Cell Carcinoma

Author:

Wu Yue12,Wei Xian12,Feng Huan12,Hu Bintao12,Liu Bo3,Luan Yang12,Ruan Yajun12,Liu Xiaming12,Liu Zhuo12,Liu Jihong12,Wang Tao12ORCID

Affiliation:

1. Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei, China

2. Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei, China

3. Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei, China

Abstract

The imbalance of the redox system has been shown to be closely related to the occurrence and progression of many cancers. However, the biological function and clinical significance of redox-related genes (RRGs) in clear cell renal cell carcinoma (ccRCC) are unclear. In our current study, we downloaded transcriptome data from The Cancer Genome Atlas (TCGA) database of ccRCC patients and identified the differential expression of RRGs in tumor and normal kidney tissues. Then, we identified a total of 344 differentially expressed RRGs, including 234 upregulated and 110 downregulated RRGs. Fourteen prognosis-related RRGs (ADAM8, CGN, EIF4EBP1, FOXM1, G6PC, HAMP, HTR2C, ITIH4, LTB4R, MMP3, PLG, PRKCG, SAA1, and VWF) were selected out, and a prognosis-related signature was constructed based on these RRGs. Survival analysis showed that overall survival was lower in the high-risk group than in the low-risk group. The area under the receiver operating characteristic curve of the risk score signature was 0.728 at three years and 0.759 at five years in the TCGA cohort and 0.804 at three years and 0.829 at five years in the E-MTAB-1980 cohort, showing good predictive performance. In addition, we explored the regulatory relationships of these RRGs with upstream miRNA, their biological functions and molecular mechanisms, and their relationship with immune cell infiltration. We also established a nomogram based on these prognostic RRGs and performed internal and external validation in the TCGA and E-MTAB-1980 cohorts, respectively, showing an accurate prediction of ccRCC prognosis. Moreover, a stratified analysis showed a significant correlation between the prognostic signature and ccRCC progression.

Funder

Medical Youth Top Talent Program of Hubei Province

Publisher

Hindawi Limited

Subject

Cell Biology,Aging,General Medicine,Biochemistry

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