Sphingosine-1-phosphate receptor 1 (S1PR1) expression in non-muscle invasive urothelial carcinoma: Association with poor clinical outcome and potential therapeutic target. Issue 14 (September 2015)

• Record Type: Journal Article
• Authors: Go, Heounjeong; Kim, Pil-Jong; Jeon, Yoon Kyung; Cho, Yong Mee; Kim, Kyungeun; Park, Bong-Hee; Ku, Ja Yoon
• Is Part Of: European journal of cancer. Volume 51:Issue 14(2015:Sep.)
• Page Start: 1937
• Page End: 1945
• Publication Date: 2015-09
• Subjects: Sphingosine-1-phosphate receptor 1 -- Non-muscle invasive urothelial carcinoma -- Prognosis -- Cancer-specific survival -- Prediction -- p53 -- Survivin; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2015.07.021
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Aim: Sphingosine-1-phosphate receptor 1 (S1PR1) promotes tumour cell survival, invasion, anti-apoptosis, metastasis and radio/chemo-resistance in various cancers. However, the expression pattern and prognostic implications of S1PR1 in urothelial carcinoma remain unclear and thus were addressed here. Methods: Tissue microarrays composed of 395 initially diagnosed and transurethral resected urothelial carcinomas of the urinary bladder were immunostained for S1PR1 and phosphor-signal transducer and activator of transcription 3 (pSTAT3). S1PR1 expression was analysed according to clinicopathological features, expression of several anti-apoptosis/proliferation-related markers and patient's survival. Results: S1PR1 positivity was observed in 45.3% of urothelial carcinomas. Among patients with non-muscle invasive urothelial carcinoma (NMIC), S1PR1 positivity was associated with higher grade ( P < 0.001), higher subepithelial invasive component ( P = 0.006), lower papillary component ( P = 0.002), presence of metastasis ( P = 0.042) and high cancer-specific death ( P < 0.001). S1PR1 expression was correlated with pSTAT3 ( P < 0.001), survivin ( P = 0.008) and Ki-67 ( P < 0.001) expression. S1PR1 positivity predicted a shorter cancer-specific survival (CSS) in NMICs ( P < 0.001) and stage T1/high grade (T1HG) tumours ( P = 0.002). The Cox multivariate model was composed of S1PR1, survivin, lymphovascular invasion and age, and C-index was 0.781. S1PR1 positivity was correlated with shorter CSS in p53-positive T1HG carcinoma ( P = 0.003) in contrast to p53-negative T1HG carcinoma ( P = 0.205). In p53-overexpressing NMIC, S1PR1 was the only variable of the survival model and the C-index was 0.719. Conclusions: S1PR1 expression was associated with unfavourable clinicopathological features and the expression of several anti-apoptosis/proliferation-related markers in urothelial carcinoma. S1PR1 serves as an independent predictor of cancer-specific death in NMIC. The model including S1PR1 showed highly accurate prediction for CSS in NMIC patients regardless of the modality of adjuvant therapy.