title: Expression and role of GPR87 in urothelial carcinoma of the bladder.
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.
authors.affiliation: Department of Urology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. kakehi@med.kagawa-u.ac.jp.
authors.forename: Homare
authors.initials: H
authors.lastname: Okazoe
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: Dage
authors.initials: D
authors.lastname: Liu
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Shibuya
authors.forename: Nobufumi
authors.initials: N
authors.lastname: Ueda
authors.forename: Mikio
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kakehi
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D015999:Multivariate Analysis; D034741:RNA, Small Interfering / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics* / Q000378:metabolism; D012008:Recurrence; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*; D019459:Urothelium / Q000378:metabolism* / Q000473:pathology
chemical_list: C526276:GPR87 protein, human; D019394:Ki-67 Antigen; D034741:RNA, Small Interfering; D049368:Receptors, Lysophosphatidic Acid