进展或转移性肾癌患者即使在给予靶向治疗药物后仍会发生疾病进展，因此探究肾癌进展的分子机制对改善肾癌患者预后至关重要。本课题组前期研究表明Gankyrin的表达结合TNM分期及SSIGN评分等可更准确地评估肾癌患者预后（Ebiomedicine），并初步阐明Gankyrin不仅可通过Hippo通路促进肾癌进展，还促进肾癌与肿瘤相关巨噬细胞（TAMs）的相互作用。本项目拟在前期基础上进一步研究：1）基于多中心临床样本及随访数据构建准确评估肾癌患者预后的Gankyrin-TAMs评价体系；2）通过转录组测序、抗体芯片检测及分子生物学实验等探究Gankyrin调控肾癌与TAMs的相互作用，以及上述效应对肾癌进展的作用机制；3）通过构建原位肾癌耐药模型验证上述机制中关键节点的靶向治疗效果。本项目将为阐明肾癌进展、肾癌与TAMs相互作用的分子机制以及寻找肾癌的有效治疗靶点提供新的科学依据。

Even patients with advanced or metastatic renal cell carcinoma (RCC) have been treated with targeted drugs, eventually most RCC patients would develop disease progression. Therefore, elucidation of the molecular mechanism underlying RCC progression is essential to improving the prognosis of patients. Our previous study demonstrated that Gankyrin expression combined with TNM staging, SSIGN score and so on could more accurately gage the prognosis of RCC patients (Ebiomedicine), and preliminary demonstrated that Gankyrin could not only promote RCC progression via regulating the Hippo pathway, but also facilitate the interaction between RCC and tumor-associated macrophages (TAMs). In the current project, we will carry out further research on the basis of the previous work: 1) Constructing a comprehensive evaluation system (Gankyrin-TAMs) which serves to assess prognosis of RCC patients based on clinical samples and the follow-up data in multi-centers; 2) Clarifying the mechanism how Gankyrin regulates RCC progression through the interaction between RCC and TAMs, and the effects on the progression of RCC by performing transcriptome analysis, antibody microarrays, molecular biological experiments and so on; 3) Establishing an animal model of orthotopic RCC with drug-resistance to verify the targeted therapeutic effects of the key nodes in the above described mechanism. The project will provide new insights into the molecular mechanisms underlying RCC progression and the interaction between RCC and TAMs and will likely identify effective therapeutic targets for RCC treatment.