Zhou F Q, Qi Y M, Xu H, Wang Q Y, Gao X S, Guo H G
Department of General Surgery, Shandong Province Binzhou People's Hospital, Binzhou, Shandong, China
Department of Gastroenterology, Shandong Province Binzhou People's Hospital, Binzhou, Shandong, China.
Genet Mol Res. 2015 May 4;14(2):4485-94. doi: 10.4238/2015.May.4.6.
The aims of this study were to explore the correlation between the expression of EpCAM and the Wnt/β-catenin pathway in human colon cancer and its clinical significance for the evaluation of cancer prognosis. Samples from colon cancer, para-carcinoma, or benign intestinal tissue from individual patients (50) and from normal intestinal mucosal tissues (20) were obtained from the Pathology Department of the Shandong Province Binzhou People's Hospital (Shandong, China). Immunohistochemistry was used to detect the expression levels of EpCAM and β-catenin proteins in these tissues, and the prognoses of the patients from whom the samples were derived were determined on follow-up examination. The corresponding in vitro mechanistic siRNA experiments were subsequently performed in the human colon cancer cell line HCT116 to observe the regulatory effects of silencing EpCAM expression on the Wnt/β-catenin pathway. From these analyses, we determined that the expression levels of EpCAM and β-catenin were higher in cancer tissues compared with other tissues from the same patient, and that the expression of EpCAM and Wnt/β- catenin in colon cancers were positively correlated. The prognostic analysis showed an inverse correlation between EpCAM and Wnt/β- catenin expression and patient prognosis. A further examination of cellular mechanisms confirmed that the silencing of EpCAM led to decreased expression of Wnt/β-catenin, and thus reduced proliferation and increased the apoptosis ratio in the cells. These results suggest that suppression of EpCAM might be a new approach for treating colon cancer.
本研究旨在探讨人结肠癌中EpCAM表达与Wnt/β-连环蛋白通路之间的相关性及其对癌症预后评估的临床意义。从山东省滨州市人民医院(中国山东)病理科获取了50例个体患者的结肠癌、癌旁组织或良性肠组织样本以及20例正常肠黏膜组织样本。采用免疫组织化学法检测这些组织中EpCAM和β-连环蛋白的表达水平,并通过随访检查确定样本来源患者的预后情况。随后在人结肠癌细胞系HCT116中进行了相应的体外机制siRNA实验,以观察沉默EpCAM表达对Wnt/β-连环蛋白通路的调控作用。通过这些分析,我们确定与同一患者的其他组织相比,癌组织中EpCAM和β-连环蛋白的表达水平更高,并且结肠癌中EpCAM与Wnt/β-连环蛋白的表达呈正相关。预后分析显示EpCAM和Wnt/β-连环蛋白表达与患者预后呈负相关。对细胞机制的进一步研究证实,沉默EpCAM会导致Wnt/β-连环蛋白表达降低,从而减少细胞增殖并增加细胞凋亡率。这些结果表明,抑制EpCAM可能是治疗结肠癌的一种新方法。