J Cancer 2021; 12(14):4134-4147. doi:10.7150/jca.53760

Research Paper

Prognostic Role of the Ubiquitin Proteasome System in Clear Cell Renal Cell Carcinoma: A Bioinformatic Perspective

Hongda Guo1,2, Yan Li1,2, Yaxiao Liu1,2, Lipeng Chen1,2, Zhengdong Gao1,2, Lekai Zhang1,2, Nan Zhou1,2, Hu Guo1,2✉, Benkang Shi1,2✉

1. Department of Urology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, China.
2. Key Laboratory of Urinary Precision Diagnosis and Treatment in Universities of Shandong, Jinan, P.R. China.

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Citation:
Guo H, Li Y, Liu Y, Chen L, Gao Z, Zhang L, Zhou N, Guo H, Shi B. Prognostic Role of the Ubiquitin Proteasome System in Clear Cell Renal Cell Carcinoma: A Bioinformatic Perspective. J Cancer 2021; 12(14):4134-4147. doi:10.7150/jca.53760. Available from https://www.jcancer.org/v12p4134.htm

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Abstract

Background: Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the urinary system. The ubiquitin proteasome system (UPS) plays an important role in the generation, metabolism and survival of tumor. We are aimed to make a comprehensive exploration of the UPS's role in ccRCC with bioinformatic tools, which may contribute to the understanding of UPS in ccRCC, and give insight for further research.

Methods: The UPS-related genes (UPSs) were collected by an integrative approach. The expression and clinical data were downloaded from TCGA database. R soft was used to perform the differentially expressed UPSs analysis, functional enrichment analysis. We also estimated prognostic value of each UPS with the help of GEPIA database. Two predicting models were constructed with the differentially expressed UPSs and prognosis-related genes, respectively. The correlations of risk score with clinical characteristics were also evaluated. Data of GSE29609 cohort were obtained from GEO database to validate the prognostic models.

Results: We finally identified 91 differentially expressed UPSs, 48 prognosis related genes among them, and constructed a prognostic model with 18 UPSs successfully, the AUC was 0.760. With the help of GEPIA, we found 391 prognosis-related UPSs, accounting for 57.84% of all UPSs. Another prognostic model was constructed with 28 prognosis-related genes of them, and with a better AUC of 0.825. Additionally, our models can also stratify patients into high and low risk groups accurately in GSE29609 cohort. Similar prognostic values of our models were observed in the validated GSE29609 cohort.

Conclusions: UPS is dysregulated in ccRCC. UPS related genes have significant prognostic value in ccRCC. Models constructed with UPSs are effective and applicable. An abnormal ubiquitin proteasome system should play an important role in ccRCC and be worthy of further study.

Keywords: the ubiquitin proteasome system (UPS), clear cell renal cell carcinoma (ccRCC), prognosis, bioinformatics