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

PeerJ

article

Sheng Ma¹  Yue Ge¹  Zezhong Xiong¹  Yanan Wang¹  Le Li¹  Zheng Chao¹  Beining Li¹  Junbiao Zhang¹  Siquan Ma¹  Jun Xiao²  Bo Liu³  Zhihua Wang¹ 

[1] Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology;Department of Thyroid and Breast Surgery, Tongji Medical College, Huazhong University of Science and Technology;Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

关键词: Oxidative stress;    UCN;    Biomarker;    Clear cell renal cell carcinoma;    Prognosis;   

DOI  :  10.7717/peerj.14784

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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.

【 授权许可】

CC BY