Overexpression levels of cripto-1 predict poor prognosis in patients with prostate cancer following radical prostatectomy

Abstract

Overexpression of cripto-1 (CR-1), an epidermal growth factor-cripto-1/FRL-1/Cryptic family protein, has been reported in multiple types of malignancy. However, the clinical functions of CR-1 in prostate cancer (PCa) remain largely unclear. The objective of the present study was to investigate the association between CR-1 expression and the clinicopathological features and prognosis of PCa. CR-1 expression was evaluated in 138 PCa tissues and 67 benign prostate hyperplasia (BPH) tissues using immunohistochemistry. The association between the clinicopathological features of patients with PCa and CR-1 expression was analyzed using a χ2 test. Receiver operating characteristic (ROC) curve and Cox regression model were used to analyze the association between CR-1 expression and biochemical recurrence (BCR)-free survival. It was revealed that the protein expression of CR-1 was markedly higher in PCa tissues than in BPH tissues. The mRNA expression of CR-1 in PCa tissue and cells was also significantly higher than in BPH tissue and the normal RWPE-1 prostate cell line (P<0.05). In addition, high CR-1 expression was significantly associated with pros-tate-specific antigen level (P=0.008), Gleason score (P=0.011) and lymph node metastasis (P=0.025) in patients with PCa. ROC curve indicated that patients with elevated expression of CR-1 exhibited shorter BCR-free survival (P<0.001). Furthermore, multivariate statistical analysis demonstrated that overexpression of CR-1 may be a novel predictor for prognosis of patients with PCa. Accordingly, the present study considered CR-1 to be a valuable predictor of poor prognosis and progression in PCa, and a potential therapeutic target for patients with PCa.