A novel gene signature related to oxidative stress predicts the prognosis in clear cell renal cell carcinoma

Sheng Ma; Yue Ge; Zezhong Xiong; Yanan Wang; Le Li; Zheng Chao; Beining Li; Junbiao Zhang; Siquan Ma; Jun Xiao; Bo Liu; Zhihua Wang

doi:10.7717/peerj.14784

A novel gene signature related to oxidative stress predicts the prognosis in clear cell renal cell carcinoma

PeerJ. 2023 Feb 8:11:e14784. doi: 10.7717/peerj.14784. eCollection 2023.

Authors

Sheng Ma^#¹, Yue Ge^#¹, Zezhong Xiong¹, Yanan Wang¹, Le Li¹, Zheng Chao¹, Beining Li¹, Junbiao Zhang¹, Siquan Ma¹, Jun Xiao², Bo Liu³, Zhihua Wang¹

Affiliations

¹ Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
² Department of Thyroid and Breast Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
³ Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

^# Contributed equally.

Abstract

Clear cell renal cell carcinoma (ccRCC) is considered to be related to the worse prognosis, which might in part be attributed to the early recurrence and metastasis, compared with other type of kidney cancer. Oxidative stress refers to an imbalance between production of oxidants and antioxidant defense. Accumulative studies have indicated that oxidative stress genes contribute to the tumor invasion, metastasis and drug sensitivity. However, the biological functions of oxidative stress genes in ccRCC remain largely unknown. In this study, we identified 1,399 oxidative stress genes from GeneCards with a relevance score ≥7. Data for analysis were accessed from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database, and were utilized as training set and validation set respectively. Univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox were employed to construct a prognostic signature in ccRCC. Finally, a prognostic signature including four different oxidative stress genes was constructed from 1,399 genes, and its predictive performance was verified through Kaplan-Meier survival analysis and the receiver operating characteristic (ROC) curve. Interestingly, we found that there was significant correlation between the expression of oxidative stress genes and the immune infiltration and the sensitivity of tumor cells to chemotherapeutics. Moreover, the highest hazard ratio gene urocortin (UCN) was chosen for further study; some necessary vitro experiments proved that the UCN could promote the ability of ccRCC proliferation and migration and contribute to the degree of oxidative stress. In conclusion, it was promising to predict the prognosis of ccRCC through the four oxidative stress genes signature. UCN played oncogenic roles in ccRCC by influencing proliferation and oxidative stress pathway, which was expected to be the novel therapeutic target for ccRCC.

Keywords: Biomarker; Clear cell renal cell carcinoma; Oxidative stress; Prognosis; UCN.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma*
Carcinoma, Renal Cell* / genetics
Humans
Kidney Neoplasms* / genetics
Oxidative Stress / genetics
Prognosis

Grants and funding

This study was supported by The National Natural Science Foundation of China (82173068, 81974400). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.