肌层浸润性膀胱癌（MIBC）是膀胱癌中恶性度较高的肿瘤，目前仍缺乏准确诊断MIBC的分子标记物及评价预后的预测因子。课题组前期通过对MIBC差异蛋白分析发现泡膜蛋白COPB2异常高表达，且与膀胱癌增殖、凋亡、侵袭密切相关；通过基因芯片预测协同互作小分子蛋白NUPR1，免疫共沉淀确定两者互相结合，功能学实验提示NUPR1亦参与膀胱癌的增殖。我们推测COPB2与NUPR1互相作用共同参与MIBC的进展，拟进一步1、收集临床MIBC组织及对照，免疫组化检测COPB2与NUPR1表达差异，分析两者表达与膀胱癌患者临床特征及术后复发、存活率和化疗药物敏感性的相关性；2、完善细胞功能学研究，明确两者参与促进膀胱癌进展、侵袭和转移的机制；3、动物实验验证细胞学功能；4、通过芯片、质谱及大数据手段分析COPB2与NUPR1促进膀胱癌进展及转移的关键信号机制。通过上述研究为MIBC诊断、预后评价提供新策略。

Muscle invasive bladder cancer (MIBC) presents high rate of recurrence and progression in urinary system. There has been a lack of molecular markers for clinical diagnosis and prognosis predictors of MIBC up to now. Previously, we used proteomics tools to identify differential expressed protein in MIBC. The most highly expressed protein, coatomer subunit beta 2 (COPB2), has been indicated to play a central role in bladder cancer cell proliferation, invasion and apoptosis. Additionally, we utilized gene chip to explore the interacting protein of COPB2. Combined with immunoprecipitation, we demonstrated that nuclear protein 1 (NUPR1) was the mutual protein of COPB2. Our functional experiments suggested that NUPR1 was also involved in the proliferation of bladder cancer. Based on these findings, we presumed that both COPB2 and NUPR1 participate in the progress of MIBC. To verify this hypothesis, we are going to: (1) explore the expression of COPB2/NUPR1 in MIBC, non-MIBC and control tissues by immunohistochemistry; (2) confirm whether both of them participate in MIBC proliferation, invasion and metastasis via in vitro experiments; (3) conduct animal experiments to verify the results of in vitro ones; (4) use Mass spectrometry combined with functional complementation to determine the specific mechanisms in the process of MIBC. The aim of the present study was to identify an independent molecular marker to predict bladder cancer outcome. It is also expected to provide a theoretical basis for new targeted drugs to treat MIBC.