Development of an Individualized Ubiquitin Prognostic Signature for Clear Cell Renal Cell Carcinoma.

Yue Wu,Tao Wang,Bintao Hu,Yang Luan,Bo Liu,Yajun Ruan,Xi Zhang,Zhiyao Deng,Xiaming Liu,Huan Feng,Jihong Liu,Zhuo Liu,Xian Wei

doi:10.3389/fcell.2021.684643

Abstract

Clear cell renal cell carcinoma (ccRCC) is a common tumor type in genitourinary system and has a poor prognosis. Ubiquitin dependent modification systems have been reported in a variety of malignancies and have influenced tumor genesis and progression. However, the molecular characteristics and prognostic value of ubiquitin in ccRCC have not been systematically reported. In our study, 204 differentially expressed ubiquitin related genes (URGs) were identified from The Cancer Genome Atlas (TCGA) cohort, including 141 up-regulated and 63 down-regulated URGs. A total of seven prognostic related URGs (CDCA3, CHFR, CORO6, RNF175, TRIM72, VAV3, and WDR72) were identified by Cox regression analysis of differential URGs and used to construct a prognostic signature. Kaplan-Meier analysis confirmed that high-risk patients had a worse prognosis (P = 1.11e-16), and the predicted area under the receiver operating characteristic (ROC) curves were 0.735 at 1 year, 0.702 at 3 years, and 0.744 at 5 years, showing good prediction accuracy. Stratified analysis showed that the URGs-based prognostic signature could be used to evaluate tumor progression in ccRCC. Further analysis confirmed that the signature is an independent prognostic factor related to the prognosis of ccRCC patients, which may help to reveal the molecular mechanism of ccRCC and provide potential diagnostic and prognostic markers for ccRCC.

Highlights

Renal cell carcinoma (RCC) is one of the most aggressive genitourinary tumors, accounting for about 4% of adult malignancies (Zhai et al, 2019)
In this study, we systematically explored the molecular characteristics and prognostic potential of these ubiquitin related genes (URGs) in Clear cell renal cell carcinoma (ccRCC), and preliminarily revealed the complex biological functions and immune processes involved in these molecules as well as their regulatory networks
Since the molecular characteristics associated with ubiquitin and their prognostic potential in ccRCC are still unclear, we comprehensively explored the key role and clinical significance of URGs in ccRCC

Summary

Introduction

Renal cell carcinoma (RCC) is one of the most aggressive genitourinary tumors, accounting for about 4% of adult malignancies (Zhai et al, 2019). Clear cell renal cell carcinoma (ccRCC) is the most studied and common. Ubiquitin Related Signature for ccRCC subtype of RCC, accounting for approximately 80% of all RCC (Escudier et al, 2019). CcRCC is a malignant and substantial tumor originating from proximal renal tubular epithelial cells, with high metastasis rate and poor prognosis. The 5-year survival rate for advanced ccRCCs is only 11.7% (Siegel et al, 2017). About 30% of patients with metastatic ccRCC at the time of initial diagnosis, and approximately 30% of patients relapse after complete removal of the primary tumor (Motzer et al, 2008; Nerich et al, 2014). A comprehensive understanding of the pathogenesis of ccRCC, identification of biomarkers, and development of effective early screening and diagnosis methods are of great significance for prognosis prediction and treatment of ccRCC

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