Rashed Hayam E, Hussein Samia, Mosaad Hala, Abdelwahab Mai M, Abdelhamid Mohamed I, Mohamed Salem Y, Mohamed Abdel Motaleb, Fayed Alaa
Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Cancer Biomark. 2017 Jul 19;20(1):107-122. doi: 10.3233/CBM-170034.
Epithelial-mesenchymal transition (EMT) is one of the main events in colorectal cancer (CRC) spread. Snail-1 is a zinc transcription factor that mediates EMT in tumor cells probably by down-regulation of E-cadherin and claudin-1.
To detect the expression of epithelial markers (claudin-1 and E-cadherin) and mesenchymal markers (snail-1 and vimentin) in primary cancer colon. Also, to select stage II cancer patients of a high risk that can benefit from postoperative adjuvant chemotherapy.
Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analysis were performed to investigate snail-1, claudin-1, E-cadherin and vimentin expressions at mRNA and protein levels in fresh tissues of cancer colon and normal colonic mucosa. The correlations between the expression of these markers and clinicopathological parameters were performed.
Normal colonic mucosa revealed complete membranous expression of claudin-1, preserved E-cadherin and negative snail-1 and vimentin expressions. Compared to control, the expression of snail-1 and vimentin mRNA in cancer colon was significantly up-regulated while the expression of claudin-1 and E-cadherin mRNA was significantly down-regulated. These changes were significantly associated with stage and lymph node involvement at both mRNA and protein levels (p< 0.05). There were significant negative correlations between vimentin and each of E-cadherin and claudin-1 gene expression and between snail-1 and each of E-cadherin and claudin-1 gene expression. Moreover, these changes were independent predictors of recurrence of stage II cancer colon cases.
There is a clinical significance of snail-1, claudin-1, E-cadherin and vimentin as possible markers for recognizing patients with lymph node involvement, advanced stage and high incidence of tumor recurrence in cancer colon.
上皮-间质转化（EMT）是结直肠癌（CRC）扩散的主要事件之一。Snail-1是一种锌转录因子，可能通过下调E-钙黏蛋白和紧密连接蛋白-1介导肿瘤细胞的EMT。
检测原发性结肠癌中上皮标志物（紧密连接蛋白-1和E-钙黏蛋白）和间质标志物（Snail-1和波形蛋白）的表达。此外，筛选出可从术后辅助化疗中获益的高危II期癌症患者。
采用逆转录-聚合酶链反应（RT-PCR）和免疫组织化学分析，研究结肠癌新鲜组织和正常结肠黏膜中Snail-1、紧密连接蛋白-1、E-钙黏蛋白和波形蛋白在mRNA和蛋白水平的表达。分析这些标志物的表达与临床病理参数之间的相关性。
正常结肠黏膜显示紧密连接蛋白-1完全呈膜性表达，E-钙黏蛋白表达保留，Snail-1和波形蛋白表达阴性。与对照组相比，结肠癌中Snail-1和波形蛋白mRNA的表达显著上调，而紧密连接蛋白-1和E-钙黏蛋白mRNA的表达显著下调。这些变化在mRNA和蛋白水平均与分期和淋巴结受累显著相关（p<0.05）。波形蛋白与E-钙黏蛋白和紧密连接蛋白-1基因表达之间以及Snail-1与E-钙黏蛋白和紧密连接蛋白-1基因表达之间均存在显著负相关。此外，这些变化是II期结肠癌病例复发的独立预测因素。
Snail-1、紧密连接蛋白-1、E-钙黏蛋白和波形蛋白作为识别结肠癌淋巴结受累、晚期及肿瘤复发高风险患者的可能标志物具有临床意义。
