下腔静脉癌栓取出术是泌尿外科风险极高的术式之一，且下腔静脉癌栓的高度决定手术难度，并与围手术期并发症发生率密切相关。术前靶向治疗可通过缩短癌栓高度来降低手术风险。本课题组前期研究发现约40%的患者对术前靶向治疗耐药，癌栓高度无变化甚至进展。预实验研究发现S100A4基因及上皮间质转化（EMT）相关分子在靶向治疗耐药组中异常升高，推测S100A4表达失调及EMT是诱导癌栓靶向治疗耐药的关键因素，但其机制不明。本课题组前期研究发现E2F1异常激活可促使肾细胞癌恶性进展及远处转移，且生物信息学预测S100A4存在E2F1启动子区域结合位点。本课题组拟在前期研究基础上进一步阐明E2F1调控S100A4诱导肾癌下腔静脉癌栓术前靶向耐药的分子机制，为提高癌栓术前靶向治疗有效率寻找新的分子靶点，最终降低手术风险并改善患者生存预后。

Inferior vena cava tumor thrombectomy is one of the most high-risk urological procedures, and the IVC tumor thrombus level influences the difficulty of surgery and is closely related to the incidence of perioperative period complications.Preoperative targeted therapy can reduce the risk of surgery by shortening the level of the tumor thrombus. Our group previously found that about 40% of patients were resistant to preoperative targeted therapy, and the tumor thrombus level did not change or even progress. Our pre-experimental study found that S100A4 gene and molecules that related to epithelial-mesenchymal transition (EMT) were abnormally elevated in the targeted drug-resistant group. It is speculated that the abnormal expression of S100A4 and process of EMT are the key factors in inducing drug resistance of tumor-targeted therapy, but its mechanism remains unclear. Our group previously found that abnormal activation of E2F1 can promote malignant progression and distant metastasis of renal cell carcinoma, and bioinformatics analysis predicts that there exists an E2F1 promoter region binding site in S100A4. Based on the previous work, our group intends to further elucidate the molecular mechanism of E2F1 regulation of S100A4-induced preoperative targeted therapy resistance of the renal cell carcinoma IVC tumor thrombus, and to find new molecular targets for improving the efficiency of preoperative targeted therapy of IVC tumor thrombus, ultimately reducing the risk of surgery and improving the survival of patients.