Wang Kaiyuan, Zheng Yu, Yang Yinli, Wang Jian, Li Baihui, Wei Feng, Zhao Hongwei, Ren Xiubao
Key Laboratory of Cancer Prevention and Therapy of Tianjin, Department of Immunology, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Key Laboratory of Cancer Prevention and Therapy of Tianjin, Department of Anesthesiology, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Front Oncol. 2019 Apr 5;9:235. doi: 10.3389/fonc.2019.00235. eCollection 2019.
Classic opioid receptors, mu (μ), delta (δ), and kappa (κ), have been reported to be expressed in non-small cell lung cancer (NSCLC) cell lines and tumor tissues and to play a role in tumor prognosis. However, the expression and role of the non-classic opioid receptor, nociceptin receptor (NOP) in cancer are unclear. Our hypothesis was that NOP was also highly expressed in NSCLC tumor tissues and this could be correlated with patients' prognostic characters. Expression of NOP was examined in archived cancer tissues from 129 enrolled NSCLC patients by immunohistochemistry and was further analyzed with the patients' outcomes. NOP expression in NSCLC cell lines was also detected. The dataset from Kaplan-Meier Plotter was used to explore the correlation between the levels of NOP mRNA in cancerous tissue and the prognosis of NSCLC patients. Cell functional assays were performed to detect the effect of NOP activation on tumor aggressive furthers. Results showed NOP expression was highly expressed in cancer tissues and human cancer cell lines. NOP expression was not associated with patients' opioid requirement but closely with some clinicopathological indicators which reflected the malignancy. Moreover, NOP staining level was the independent poor prognostic factor for NSCLC patients receiving lobectomy, which was further verified by determining the mRNA expression levels through the online dataset. experiments revealed that NOP activation promotes the proliferation and invasion of A549 cells via PI3K/Akt signaling pathway. We conclude that NOP is overexpressed in NSCLC and is inversely correlated with patient's postoperative survival.
据报道，经典阿片受体，即μ、δ和κ受体，在非小细胞肺癌（NSCLC）细胞系和肿瘤组织中表达，并在肿瘤预后中发挥作用。然而，非经典阿片受体——孤啡肽受体（NOP）在癌症中的表达和作用尚不清楚。我们的假设是，NOP在NSCLC肿瘤组织中也高表达，且这可能与患者的预后特征相关。通过免疫组织化学检测了129例入组NSCLC患者存档癌组织中NOP的表达，并进一步分析了患者的预后情况。还检测了NSCLC细胞系中NOP的表达。利用Kaplan-Meier Plotter数据集探讨癌组织中NOP mRNA水平与NSCLC患者预后的相关性。进行细胞功能试验以进一步检测NOP激活对肿瘤侵袭性的影响。结果显示，NOP在癌组织和人癌细胞系中高表达。NOP表达与患者的阿片类药物需求无关，但与一些反映恶性程度的临床病理指标密切相关。此外，NOP染色水平是接受肺叶切除术的NSCLC患者独立的不良预后因素，通过在线数据集确定mRNA表达水平进一步证实了这一点。实验表明，NOP激活通过PI3K/Akt信号通路促进A549细胞的增殖和侵袭。我们得出结论，NOP在NSCLC中过表达，且与患者术后生存率呈负相关。
