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Expression and Role of GPR87 in Urothelial Carcinoma of the Bladder
Department of Urology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan
Department of General Thoracic Surgery, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan
Department of Diagnostic Pathology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan
* Author to whom correspondence should be addressed.
Received: 22 April 2013; in revised form: 1 June 2013 / Accepted: 3 June 2013 / Published: 10 June 2013
Abstract: The orphan GPR87 has recently been matched with its ligand LPA, which is a lipid mediator with multiple physiological functions, including cancer cell proliferation. This study aimed to clarify the role of GPR87 in urothelial carcinoma of the bladder. GPR87 expression was assessed in seven human bladder cancer cell lines. A replication-deficient recombinant adenoviral vector expressing shRNA targeting GPR87 (Ad-shGPR87), was constructed. Gene silencing was carried out using Ad-shGPR87. Immunohistochemical analysis was performed for transurethral resection of bladder tumor samples from 71 patients with non-muscle-invasive bladder cancer. We observed GPR87 expression in five of the seven cell lines, and silencing GPR87 gene expression significantly reduced cell viability. GPR87 expression was positive in 38 (54%) of 71 tumors. Ki-67 index was associated with positive GPR87 staining status (p < 0.0001). Patients with GPR87-positive tumors had shorter intravesical recurrence-free survival than those with GPR87-negative tumors (p = 0.010). Multivariate analysis revealed that GPR87 staining status was an independent prognostic parameter for intravesical recurrence (p = 0.041). Progression from non-muscle-invasive to muscle-invasive tumor was more frequently observed in patients with GPR87-positive tumors, although this trend did not reach statistical significance (p = 0.056). These results warrant further prospective studies to clarify the role of GPR87 expression in intravesical recurrence and progression in bladder cancer.
Keywords: GPR87; non-muscle-invasive bladder cancer; intravesical recurrence; progression
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Okazoe, H.; Zhang, X.; Liu, D.; Shibuya, S.; Ueda, N.; Sugimoto, M.; Kakehi, Y. Expression and Role of GPR87 in Urothelial Carcinoma of the Bladder. Int. J. Mol. Sci. 2013, 14, 12367-12379.
Okazoe H, Zhang X, Liu D, Shibuya S, Ueda N, Sugimoto M, Kakehi Y. Expression and Role of GPR87 in Urothelial Carcinoma of the Bladder. International Journal of Molecular Sciences. 2013; 14(6):12367-12379.
Okazoe, Homare; Zhang, Xia; Liu, Dage; Shibuya, Shinsuke; Ueda, Nobufumi; Sugimoto, Mikio; Kakehi, Yoshiyuki. 2013. "Expression and Role of GPR87 in Urothelial Carcinoma of the Bladder." Int. J. Mol. Sci. 14, no. 6: 12367-12379.