紧密连接蛋白claudin-4在肾透明细胞癌中的表达及预后意义

Expression of Claudin-4 in Human Clear-cell Renal Cell Carcinoma and its Relationship with Clinical Pathology and Prognosis

目的：探讨claudin-4在肾透明细胞癌中的表达及与临床病理特征及预后的相关性。方法：应用免疫组织化学技术检测50例肾透明细胞癌组织及10例正常肾组织标本中claudin-4的表达情况,并分析与临床病理参数的相关性;随机选取其中4例肾透明细胞癌患者癌组织及4例正常肾新鲜组织,Western blot检测claudin-4的表达情况,并与免疫组化检测结果进行相关性分析;结合随访结果分析claudin-4的表达水平与患者无疾病生存期的关系。结果：Claudin-4在肾透明细胞癌组织中的表达显著高于肾正常组织（P〈0.05）,表达水平与肿瘤的直径、TNM分期、临床分期及淋巴结转移相关;Western blot结果也表明claudin-4在肾透明细胞癌组织中的表达显著高于肾正常组织（P〈0.01）,与免疫组化结果呈显著正相关（r2=0.748,P〈0.01）;Kaplan-Meier分析显示claudin-4高表达组患者的患者无疾病生存期为20.7个月,显著低于低表达组的30.8个月。COX多因素比例风险模型分析显示,claudin-4的表达不是肾透明细胞癌的独立预后因素（RR值=1.686,95%CI 0.174~16.311,P=0.652）。结论：claudin-4蛋白表达上调可能促进肾透明细胞癌的发生和发展,有可能作为肾透明细胞癌潜在的治疗靶点及影响不良预后的指标。

Objective： To investigate the expressions of claudin-4 in human clear-cell renal cell carcinoma（cc RCC）, and its relationship with clinical pathology and prognosis. Methods： The expression of claudin-4 in 50 cases of cc RCC and 10 normal kidney tissues were detected by immunohistochemical staining（IHC）, analyzing the relationship between the expression level of claudin-4 and clinicopathological variables. Western blot was employed to confirm the expression of claudin-4 in 4 cases of cc RCC and 4 normal kidney tissues. The relationship of claudin-4 expression level and disease-free survival（DFS） was analyzed to predict the prognosis of cc RCC. Results： The expression level of claudin-4 in cc RCC was significantly higher than that in normal kidney tissues（P0.05） and was markedly associated with tumor diameters, T stages, clinical stages and lymph node metastasis. The result of Western blot also confirmed that the expression of claudin-4 was much higher in cc RCC than normal kidney tissues（P0.01）, which were positively correlated with the results of immunohistochemical（IHC） staining（r2=0.748, P0.01）. Furthermore, Kaplan-Meier analysis showed that elevated expression of claudin-4 was associated with worse prognosis in cc RCC. Cox proportional-hazards regression model analysis indicated that claudin-4 was not an independent prognostic factor for cc RCC patients after surgery（relative risk=1.686, 95% CI：0.174-16.311, P=0.652）. Conclusion： Claudin-4 might play a positive role in carcinogenesis and development of cc RCC, which might become a potential therapeutic target and adverse prognostic factor.