膀胱癌在我国男性泌尿生殖系统肿瘤中发病率第一，且复发率极高。膀胱肿瘤的特性决定了其肿瘤微环境在肿瘤的发生及复发过程中发挥至关重要的调控作用。我们的前期研究筛选出一种分泌蛋白因子NOV，发现其在膀胱肿瘤组织中高表达，且与肿瘤的复发直接相关。使用肿瘤上清或者体外重组蛋白rNOV处理良性膀胱肿瘤细胞RT-4能明显促进其发生恶性转化。基因芯片分析提示，rNOV处理后的RT-4细胞高表达WNT通路相关分子β-catenin、Wnt5a、Wnt6和Wnt10a。在本研究中，我们拟通过细胞验证NOV与膀胱肿瘤发生及复发的关系；通过分子生物学实验研究NOV调控WNT信号通路的分子机制；通过临床统计学分析膀胱组织、血清及尿液中的NOV表达对膀胱癌复发的预后价值；通过动物实验探讨中和清除肿瘤微环境中的NOV是否能协助膀胱灌注来降低膀胱癌的复发率，以期为膀胱癌复发提供预后的靶标和干预的靶点。

The incidence of bladder cancer is in the first placein our male urogenital,andbladder cancer has high relapse rate. The characteristics of bladder cancer tumordetermine that microenvironment plays a crucial role in the regulation and the process of tumor recurrence. Our previous study screened a secreted protein factor NOV, found its expression in bladder cancer tissues, and directly related to tumor recurrence. Use of recombinant proteins in vitro tumor supernatant or rNOV treatment of benign bladder tumor cell RT-4 can promote the occurrence of malignant transformation. Microarray analysis showed that, RT-4 cells were treated with high expression rNOV WNT pathway related molecule β-catenin, Wnt5a, Wnt6 and Wnt10a. By molecular biology molecular mechanisms regulating experimental study NOV WNT signaling pathway; through statistical analysis of clinical bladder tissue, serum and urine NOV In this study, we proposed the occurrence and recurrence relations verified by NOV and bladder cancer cells the prognostic value of the expression of bladder cancer recurrence.We want to investigate whether NOV can help to reduce the recurrence rate of intravesical bladder cancer byremoving the tumor microenvironment,NOV in animal experiment.This study aims to provide targets for intervention and prognosis for recurrence of bladder cancer.