Nii Kazuhito, Tokunaga Yoshimasa, Liu Dage, Zhang Xia, Nakano Jun, Ishikawa Shinya, Kakehi Yoshiyuki, Haba Reiji, Yokomise Hiroyasu
Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan.
Department of Urology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan.
Mol Clin Oncol. 2014 Jul;2(4):539-544. doi: 10.3892/mco.2014.292. Epub 2014 May 15.
G protein-coupled receptor 87 (GPR87) is a newly deorphanized member of the transmembrane G protein-coupled receptor family. Recently, GPR87 was suggested to contribute to the viability of human tumor cells and overexpression of GPR87 mRNA was detected in a number of malignant tumors, including lung cancer. We performed a retrospective study of GPR87 expression in association with clinical characteristics and biological markers in non-small-cell lung cancer (NSCLC). We investigated a total of 123 patients with NSCLC who underwent surgery between 1999 and 2004 (58 adenocarcinomas, 53 squamous cell carcinomas and 12 others). Immunohistochemistry was used to evaluate the intratumoral expression of GPR87 and the Ki-67 proliferation index. The TUNEL method was also used to investigate tumor apoptosis. A total of 63 tumors (51.2%) were found to be GPR87-positive. These tumors were more frequently encountered among squamous cell carcinomas rather than among adenocarcinomas (62.3 vs. 43.1%, respectively; P=0.044) and were significantly more frequently poorly and moderately differentiated rather than well differentiated (P=0.029). Moreover, the Ki-67 index was significantly higher in GPR87-positive compared to GPR87-negative tumors (57.0 vs. 40.0%, respectively; P=0.002). The overall survival was significantly worse for patients with GPR87-positive compared to those with GPR87-negative tumors (P=0.029). The Cox regression analyses also demonstrated that the GPR87 status was a significant prognostic factor for NSCLC patients [hazard ratio=2.053; P=0.018). The present study demonstrated that in NSCLC, the overexpression of GPR87 is significantly associated with poorer differentiation and higher proliferation. During the progression of NSCLC, GPR87 overexpression may be associated with the acquisition of a more aggressive phenotype and, therefore, is a potentially useful target for prognostication and treatment.
G蛋白偶联受体87（GPR87）是跨膜G蛋白偶联受体家族中一个新确定功能的成员。最近，有研究表明GPR87对人类肿瘤细胞的生存能力有影响，并且在包括肺癌在内的多种恶性肿瘤中检测到GPR87 mRNA的过表达。我们对非小细胞肺癌（NSCLC）中GPR87表达与临床特征及生物学标志物之间的关系进行了一项回顾性研究。我们共调查了1999年至2004年间接受手术的123例NSCLC患者（58例腺癌、53例鳞状细胞癌和12例其他类型）。采用免疫组织化学法评估肿瘤内GPR87的表达及Ki-67增殖指数。还采用TUNEL法研究肿瘤细胞凋亡情况。共发现63例肿瘤（51.2%）为GPR87阳性。这些肿瘤在鳞状细胞癌中比在腺癌中更常见（分别为62.3%和43.1%；P = 0.044），并且在低分化和中分化肿瘤中比高分化肿瘤更常见（P = 0.029）。此外，GPR87阳性肿瘤的Ki-67指数显著高于GPR87阴性肿瘤（分别为57.0%和40.0%；P = 0.002）。GPR87阳性患者的总生存期明显比GPR87阴性患者差（P = 0.029）。Cox回归分析也表明，GPR87状态是NSCLC患者的一个重要预后因素[风险比 = 2.053；P = 0.018]。本研究表明，在NSCLC中，GPR87的过表达与较差的分化程度和较高的增殖能力显著相关。在NSCLC的进展过程中，GPR87过表达可能与更具侵袭性的表型的获得有关，因此，它是一个潜在的预后评估和治疗有用靶点。
