Wang Yingjing, Shi Muqi, Yang Nan, Zhou Xiaoyu, Xu Liqin
Department of Clinical Biobank, Affiliated Hospital of Nantong University, Nantong, China.
Department of Pathology, Medical School of Nantong University, Nantong, China.
Front Oncol. 2020 Nov 20;10:577530. doi: 10.3389/fonc.2020.577530. eCollection 2020.
GPR115, a member of the adhesion G protein-coupled receptor family, is dysregulated in many cancers. However, the expression and function of GRP115 in non-small cell lung cancer (NSCLC) is not clear. Here, we examined the expression pattern, clinical significance, and function of GPR115 in NSCLC by analysis of clinical specimens and human cell lines and bioinformatics analysis. Immunohistochemical analysis of clinical samples showed that GPR115 was significantly upregulated in NSCLC tissues compares with normal lung epithelial tissue (P < 0.05). And GPR115 overexpression is an independent prognostic factor for 5-year overall survival of NSCLC patients [hazard ratio (HR)=1.625, P = 0.008]. Interestingly, higher expression of GPR115 was strongly correlation with differentiation level (P = 0.027), tumor size (P = 0.010), lymph node metastasis (P = 0.022), tumor-node-metastasis stage (P = 0.008), and poor prognosis of lung adenocarcinoma (LUAD, all P = 0.039), but not lung squamous cell carcinoma (LUSC, P > 0.05). Moreover, downregulation of GPR115 by RNA interference in human lung cancer lines inhibited cell proliferation, migration, and invasion. Preliminary bioinformatic analysis confirmed that GPR115 was closely associated with LAMC2 (Spearman correlation coefficient=0.67, P < 0.05), which was accumulated in ECM-receptor interaction and focal adhesion. Consistent with these findings, deceased of GPR115 was associated with E-cadherin, N-cadherin and Vimentin confirmed by western blot. In conclusion, these data suggest that GPR115 may play a role in the tumor growth and metastasis and may have utility as a diagnostic and prognostic marker for LUAD, but not LUSC.
GPR115是粘附G蛋白偶联受体家族的成员之一，在许多癌症中表达失调。然而，GRP115在非小细胞肺癌（NSCLC）中的表达和功能尚不清楚。在此，我们通过分析临床标本、人类细胞系以及进行生物信息学分析，研究了GPR115在NSCLC中的表达模式、临床意义和功能。对临床样本的免疫组织化学分析表明，与正常肺上皮组织相比，NSCLC组织中GPR115显著上调（P < 0.05）。并且GPR115过表达是NSCLC患者5年总生存期的独立预后因素[风险比（HR）=1.625，P = 0.008]。有趣的是，GPR115的高表达与分化程度（P = 0.027）、肿瘤大小（P = 0.010）、淋巴结转移（P = 0.022）、肿瘤-淋巴结-转移分期（P = 0.008）以及肺腺癌（LUAD，所有P = 0.039）的预后不良密切相关，但与肺鳞状细胞癌（LUSC，P > 0.05）无关。此外，通过RNA干扰下调人肺癌细胞系中的GPR115可抑制细胞增殖、迁移和侵袭。初步的生物信息学分析证实，GPR115与LAMC2密切相关（斯皮尔曼相关系数=0.67，P < 0.05），LAMC2在细胞外基质-受体相互作用和粘着斑中积累。与这些发现一致，蛋白质免疫印迹证实GPR115的缺失与E-钙粘蛋白、N-钙粘蛋白和波形蛋白有关。总之，这些数据表明GPR115可能在肿瘤生长和转移中起作用，并且可能作为LUAD而非LUSC的诊断和预后标志物。
