目的：探讨神经依赖性活性保护蛋白（ADNP）在膀胱尿路上皮癌中的表达情况及其临床意义。方法：收集中南大学湘雅医学院附属肿瘤医院2019 年6 月1 日至2019 年7 月15 日手术切除的膀胱癌及其配对的癌旁组织标本各28 例，采用qPCR检测20 例膀胱癌组织和癌旁组织的ADNP mRNA表达水平，WB检测其余8 对标本的ADNP蛋白表达水平。同时，回顾性分析我院2005 年1 月1 日至2007 年12 月31 日收治的膀胱尿路上皮癌患者221 例的临床病理资料，免疫组化染色方法检相应患者手术切除的石蜡标本中ADNP的表达情况，并收集同期因其他膀胱疾病而手术患者的非肿瘤膀胱组织切片用作对照。卡方检验分析ADNP表达与不同临床病理因素之间的相关性，Kaplan-Meier 法进行生存分析，Cox 比例风险回归模型对患者预后影响因素进行单因素及多因素分析。结果：膀胱尿路上皮癌组织中ADNP的转录和翻译水平均高于非肿瘤组织（均P<0.05），且ADNP的表达量与膀胱癌的组织学分级、临床分期及患者存活状态有着相关性(P<0.05）。纳入的221 例患者随访中失访32 例，ADNP高表达较低表达的膀胱患者有着不良的预后（5 年OS：49.5% vs 78.6%，P<0.01；5 年PFS：40.0% vs 72.2% ，P<0.01；10 年OS：26.6% vs 58.6% ，P<0.01；10 年PFS：25.3% vs 47.9%，P<0.01）。Cox 单因素回归模型显示，ADNP表达量与膀胱癌的预后密切相关（P<0.05）；同时Cox 多因素回归也表明ADNP表达量（95% CI：1.300~2.905，P=0.001）是影响膀胱癌预后的独立危险因素。结论：ADNP在膀胱癌组织中的表达水平比非肿瘤的膀胱组织有显著的升高，组织学分级及临床分期与ADNP的表达水平有相关性，ADNP低表达的膀胱癌患者预后相对较好,ADNP有望成为膀胱癌的特异性治疗候选靶点。

Objective：To analyze the expression and clinic significance of activity-dependent neuroprotective protein (ADNP) in bladder urothelial carcinoma. Methods: A total of 28 pairs of bladder cancer tissues and corresponding adjacent normal tissuesthat surgically resected at the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University from June 1, 2019 to July 15,2019 were collected for this study. The mRNA expression of ADNP in 20 pairs of tissue samples was detected by qPCR, and the protein expressionin the other 8 pairs was detected by WB. Mean while, the clinicopathological data of patients with bladder urothelial carcinoma treated in our hospital from January 1, 2005 to December 31, 2007 were retrospectively analyzed; and the expression of ADNP in the corresponding paraffin tumor sections were determined with immunohistochemical staining, and normal bladder tissue sections from patients who underwent surgery for other bladder diseases during the same period were collected for comparison. Chi-square test was used to analyze the correlation between ADNP expression and different clinicopathological features, Kaplan-Meier method was used for survival analysis, and Cox risk regression model was used for univariate and multivariate analysis of prognostic factors. Results:The transcriptional and translational levels ofADNPin cancer tissues were higher than those in adjacent normal tissues (all P<0.05), and the expression level of ADNP was correlated with the histological grade, clinical stages and survival status of patients with bladder cancer (P<0.05). Of all the 221 patients included in the study, 32 patients lost to follow-up,and patients with high ADNP expression had poor prognosis (5-year OS: 49.5% vs 78.6%, P<0.01; 5-year PFS: 40.0% vs 72.2%, P<0.01; 10-year OS: 26.6% vs 58.6%, P<0.01; 10-year PFS: 25.3% vs 47.9%, P<0.01). Cox univariate regression analysis showed that ADNP expression was closely related to the prognosis of bladder cancer (P<0.05); and Cox multivariate regression analysisalso showed that ADNP expression (95% CI: 1.300-2.905, P=0.001) was an independent risk factor for the prognosis of bladder cancer. Conclusion: The expression level of ADNP in bladder cancertissuesis significantly higher than that in non-tumor bladder tissues. Histological grade and clinical stageare correlated with the expression level of ADNP. The prognosis of bladder cancer patients with low ADNP expression is relatively better compared to patients with high ADNP expression, andADNP is expected to be a candidate target for specific treatment of bladder cancer.

湖南省科技厅重点研发计划项目资助（No. 2018SK2120）