Abstract
Background: Ubiquitin and ubiquitin-like (UB/UBL) conjugations are one of the most important post-translational modifications and involve in the occurrence of cancers. However, the biological function and clinical significance of ubiquitin related genes (URGs) in prostate cancer (PCa) are still unclear. Methods: The transcriptome data and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA), which was served as training cohort. The GSE21034 dataset was used to validate. The two datasets were removed batch effects and normalized using the “sva” R package. Univariate Cox, LASSO Cox, and multivariate Cox regression were performed to identify a URGs prognostic signature. Then Kaplan-Meier curve and receiver operating characteristic (ROC) curve analyses were used to evaluate the performance of the URGs signature. Thereafter, a nomogram was constructed and evaluated. Results: A six-URGs signature was established to predict biochemical recurrence (BCR) of PCa, which included ARIH2, FBXO6, GNB4, HECW2, LZTR1 and RNF185. Kaplan-Meier curve and ROC curve analyses revealed good performance of the prognostic signature in both training cohort and validation cohort. Univariate and multivariate Cox analyses showed the signature was an independent prognostic factor for BCR of PCa in training cohort. Then a nomogram based on the URGs signature and clinicopathological factors was established and showed an accurate prediction for prognosis in PCa. Conclusion: Our study established a URGs prognostic signature and constructed a nomogram to predict the BCR of PCa. This study could help with individualized treatment and identify PCa patients with high BCR risks.
Highlights
Prostate cancer (PCa) is one of the most common malignancies worldwide with the third highest cancer-causing deaths following lung cancer and colorectal cancer in American males (Schatten, 2018)
biochemical recurrence (BCR) information and transcriptome data of 427 patients were obtained from the the Cancer Genome Atlas (TCGA) database
The univariate Cox regression analysis found that the expression of 236 ubiquitin related genes (URGs) were significantly correlated with BCR prognosis of PCa patients (p < 0.05; Supplementary Table S1)
Summary
Prostate cancer (PCa) is one of the most common malignancies worldwide with the third highest cancer-causing deaths following lung cancer and colorectal cancer in American males (Schatten, 2018). Ubiquitin Related Signature for PCa after radical prostatectomy without neoadjuvant or adjuvant therapy (Liesenfeld et al, 2017). Ubiquitin and ubiquitin-like (UB/UBL) conjugations are vital post-translational modifications which participate in most biological processes and pathways such as protein degradation and turnover, intercellular signal transduction, cell cycle and DNA damage repair (Swatek and Komander, 2016). The protein containing ubiquitin-binding domain (UBDs) and ubiquitin-like domains (ULDs) plays an important role in regulating the ubiquitination process (Buchberger, 2002; Heride et al, 2014). Ubiquitin and ubiquitin-like (UB/UBL) conjugations are one of the most important post-translational modifications and involve in the occurrence of cancers. The biological function and clinical significance of ubiquitin related genes (URGs) in prostate cancer (PCa) are still unclear
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