Norrin又称诺里病蛋白，通过与FZD4和LRP5/6受体结合激活Wnt通路，在肿瘤发生发展中有重要作用。有报道称G蛋白偶联受体LGR4是Norrin的潜在受体，但Norrin/LGR4复合物是否真实存在，以及该复合物有何生物学功能还有待深入研究。前期工作中，申请人用重组蛋白验证了该复合物，并解析其结构，揭示了它的关键结合表位；组织芯片结果显示Norrin和LGR4在多种肿瘤中都高表达，而在肺癌中具有显著的表达相关性，在肺癌细胞系也得到一致的结果，这些提示Norrin/LGR4复合物在肺癌中具有重要的功能。在此基础上，本项目将从体内外实验深入研究Norrin/LGR4复合物在肺癌中的生物学功能；运用蛋白组学技术阐明其发挥作用的效应分子或关键信号通路；对肺癌患者组织样本回顾分析，揭示Norrin和LGR4的临床价值。该项目的实施，可以为肺癌的诊断和预后提供科学依据，为肺癌的治疗提供潜在靶标

Norrin, also known as Norrie disease protein. It plays an important role in tumor development by activating the canonical Wnt pathway through the Frizzled4 and LRP5/6 receptor. It has been reported that LGR4 ( Leucine-rich repeat-containing G-protein-coupled receptor 4 ) is a potential receptor for Norrin, but whether Norrin/ LGR4 complex is really exist and what’s the biological function of this complex remains to be further studied. In the preliminary study, the applicant demonstrated the complex with the recombinant protein, analyzed its structure and verified the critical binding sites. Then we applied the tissue chip, it showed that Norrin and LGR4 were highly expressed in various tumors, and the relevance expression was observed significantly in lung cancers tissues and cell lines. These results suggest that Norrin/ LGR4 complexes have important functions in lung cancers. This project aimed to reveal the biological function of Norrin/LGR4 complex in lung cancer and elucidate its effector or key signaling pathway by using proteomics technology. Futhermore, we will evaluate whether Norrin and LGR4 can be used as biomarkers for lung cancer. The implementation of this innovative project will not only provide a theoretical instruction for the diagnosis and prognosis of lung cancer, but aslo provide potential targets for the treatment of lung cancer in clinical trail.