Singh Rinni, Ansari Jamal A, Maurya Niharika, Mandhani Anil, Agrawal Vinita, Garg Minal
Department of Biochemistry, Lucknow University, Lucknow, India.
Department of Food Toxicology, Indian Institute of Toxicology Research, Lucknow, India.
Clin Genitourin Cancer. 2017 Apr;15(2):e187-e197. doi: 10.1016/j.clgc.2016.07.021. Epub 2016 Aug 9.
Epithelial-to-mesenchymal transition (EMT) is a dynamic process in the pathogenesis of urinary bladder cancer. Despite significant advancements in its diagnosis and treatment, the outcomes have more or less remained the same. In the present study, the expression of EMT markers was investigated to evaluate its prognostic significance in patients with non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC).
The present study was undertaken to examine the expression of EMT markers, including E-cadherin, N-cadherin, vimentin, Snail, Twist, Zeb, and Slug, on 28 bladder tumor tissues (15 cases of NMIBC and 13 of MIBC) using reverse transcription-polymerase chain reaction. Immunohistochemical (IHC) staining was performed to check the protein expression and localization of E-cadherin, N-cadherin, vimentin, Snail, and Slug.
At the message level, reduced expression of E-cadherin correlated with gender (P = .004), enhanced expression of N-cadherin correlated with stage and age (P = .02, for both), and increased expression of EMT transcription factors correlated significantly with stage, grade, or age. Inverse correlation of reduced levels of E-cadherin were observed with new expression of N-cadherin (P = .001; Mann-Whitney U test) and vimentin (P = .001; Mann-Whitney U test). On IHC, novel expression of vimentin and N-cadherin was associated with enhanced expression of Snail and Slug (P = .005; Wilcoxon signed rank test).
Molecular validation of the EMT marker profile proved to be a sensitive and an effective prognostic tool for objective and systematic investigation of EMT function in the pathogenesis of urinary bladder cancer. Nevertheless, further studies are required with a greater number of clinical samples.
上皮-间质转化（EMT）是膀胱癌发病机制中的一个动态过程。尽管其诊断和治疗取得了显著进展，但治疗结果或多或少仍保持不变。在本研究中，对EMT标志物的表达进行了研究，以评估其在非肌层浸润性膀胱癌（NMIBC）和肌层浸润性膀胱癌（MIBC）患者中的预后意义。
本研究采用逆转录-聚合酶链反应检测28例膀胱肿瘤组织（15例NMIBC和13例MIBC）中EMT标志物的表达，包括E-钙黏蛋白、N-钙黏蛋白、波形蛋白、Snail、Twist、Zeb和Slug。进行免疫组织化学（IHC）染色以检查E-钙黏蛋白、N-钙黏蛋白、波形蛋白、Snail和Slug的蛋白表达及定位。
在信使水平上，E-钙黏蛋白表达降低与性别相关（P = 0.004），N-钙黏蛋白表达增强与分期和年龄相关（两者P均 = 0.02），EMT转录因子表达增加与分期、分级或年龄显著相关。观察到E-钙黏蛋白水平降低与N-钙黏蛋白新表达（P = 0.001；曼-惠特尼U检验）和波形蛋白新表达（P = 0.001；曼-惠特尼U检验）呈负相关。在免疫组织化学方面，波形蛋白和N-钙黏蛋白的新表达与Snail和Slug表达增强相关（P = 0.005；威尔科克森符号秩检验）。
EMT标志物谱的分子验证被证明是一种敏感且有效的预后工具，可用于客观、系统地研究EMT在膀胱癌发病机制中的作用。然而，需要更多的临床样本进行进一步研究。
