Okazoe Homare, Zhang Xia, Liu Dage, Shibuya Shinsuke, Ueda Nobufumi, Sugimoto Mikio, Kakehi Yoshiyuki
Department of Urology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Int J Mol Sci. 2013 Jun 10;14(6):12367-79. doi: 10.3390/ijms140612367.
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.
孤儿G蛋白偶联受体87（GPR87）最近被发现与它的配体溶血磷脂酸（LPA）相匹配，LPA是一种具有多种生理功能的脂质介质，包括癌细胞增殖。本研究旨在阐明GPR87在膀胱尿路上皮癌中的作用。对七种人膀胱癌细胞系中的GPR87表达进行了评估。构建了一种表达靶向GPR87的短发夹RNA（shRNA）的复制缺陷型重组腺病毒载体（Ad-shGPR87）。使用Ad-shGPR87进行基因沉默。对71例非肌层浸润性膀胱癌患者的膀胱肿瘤经尿道切除标本进行免疫组织化学分析。我们在七种细胞系中的五种中观察到GPR87表达，并且沉默GPR87基因表达显著降低了细胞活力。71例肿瘤中有38例（54%）GPR87表达呈阳性。Ki-67指数与GPR87染色阳性状态相关（p<0.0001）。GPR87阳性肿瘤患者的膀胱内无复发生存期比GPR87阴性肿瘤患者短（p = 0.010）。多变量分析显示，GPR87染色状态是膀胱内复发的独立预后参数（p = 0.041）。在GPR87阳性肿瘤患者中更频繁地观察到从非肌层浸润性肿瘤进展为肌层浸润性肿瘤，尽管这一趋势未达到统计学显著性（p = 0.056）。这些结果需要进一步的前瞻性研究来阐明GPR87表达在膀胱癌膀胱内复发和进展中的作用。
