Neoplasma. 2017;64(1):32-39. doi: 10.4149/neo_2017_104.
G protein-coupled receptor 56 (GPR56) has been demonstrated to be a significant prognostic predictor in several types of malignances, including melanoma, glioblastoma, breast cancer, colon cancer, and pancreatic cancer. GPR56 has a putative mucin-like extracellular domain, indicating functions for this receptor in the cell-cell interactions and triggering different downstream signaling pathways responsible for regulating cell survival, proliferation, adhesion, and migration. But the expression and clinical significance of GPR56 has not been elucidated in epithelial ovarian cancer (EOC). We detected GPR56 expression by immunohistochemistry in 110 samples of ovarian serous carcinoma to explore the correlation between its expression and clinicopathologic characteristics and overall survival. As the result, we found that GPR56 expression is significantly associated with advanced FIGO stage (P = 0.01) and positive lymph node invasion (P = 0.016), and it serves as an independent unfavorable prognostic factor through univariate and multivariate analysis. GPR56 knockdown could dramatically decrease the proliferation and invasion of epithelial ovarian cancer cells through down-regulating the RhoA-GTP level and up-regulating the E-cadherin level, which indicates GPR56 could promote the progression and invasion of EOC. In conclusion, GPR56 expression was demonstrated as an independent prognostic factor in EOC, suggesting that GPR56 may play an oncogenic role through the Rho and E-cadherin pathway and GPR56 could be a novel potential drug target in EOC.
G 蛋白偶联受体 56（GPR56）已被证明是多种恶性肿瘤的重要预后预测因子，包括黑色素瘤、胶质母细胞瘤、乳腺癌、结肠癌和胰腺癌。GPR56 具有假定的粘蛋白样细胞外结构域，表明该受体在细胞-细胞相互作用中具有功能，并触发不同的下游信号通路，负责调节细胞存活、增殖、黏附和迁移。但是，GPR56 在卵巢上皮性癌（EOC）中的表达和临床意义尚未阐明。我们通过免疫组织化学检测了 110 例卵巢浆液性癌样本中的 GPR56 表达，以探讨其表达与临床病理特征和总生存的相关性。结果发现，GPR56 表达与 FIGO 晚期（P = 0.01）和阳性淋巴结浸润（P = 0.016）显著相关，并且通过单因素和多因素分析，它是一个独立的不利预后因素。GPR56 敲低通过下调 RhoA-GTP 水平和上调 E-钙黏蛋白水平，显著降低上皮性卵巢癌细胞的增殖和侵袭能力，表明 GPR56 可能通过 Rho 和 E-钙黏蛋白途径促进 EOC 的进展和侵袭。总之，GPR56 表达被证明是 EOC 的独立预后因素，表明 GPR56 可能通过 Rho 和 E-钙黏蛋白途径发挥致癌作用，GPR56 可能成为 EOC 的一个新的潜在药物靶点。
