胆管癌中Wnt2b的表达及其与上皮间质转化的关系

Expression of Wnt2b in cholangiocarcinoma and its relationship with epithelial-mesenchymal transition

目的通过观察Wnt2b信号通路与上皮间质转化(EMT)标记蛋白在胆管癌中的表达情况及其与临床特征的关系,进一步探索Wnt2b与胆管癌EMT的关系及在侵袭转移中的相关性。方法采用免疫组化染色方法检测青岛大学附属医院2008年12月至2013年12月入院的60例胆管癌及30例胆管正常组织中wnt2b、EMT标记蛋白E-cadherin和vimentin的表达情况,通过计数资料的χ^2检验分析各蛋白与临床病理特征的相关性。结果胆管癌中Wnt2b表达有54例(占90.0%),而正常胆管组织中Wnt2b表达只有1例(占3.3%),两组差异具有统计学意义(χ^2=38.1,P<0.05);Wnt2b在T3+T4期的表达阳性率明显高于T1+T2期(P<0.05),但与患者的临床特征如年龄、性别、肿瘤位置及肿瘤分化程度等没有关联(P>0.05);发生淋巴结转移的患者较无淋巴结转移患者vimentin阳性表达上调,E-cadherin的表达缺失上调,差异均有统计学意义(均P<0.05),但与患者的性别、年龄、肿瘤位置及分化程度无关(P>0.05)。胆管癌细胞中Wnt2b的表达增高与EMT标记物E-cadherin表达缺失上调、vimentin阳性表达上调具有相关性(均P<0.05)。结论Wnt2b在胆管癌组织中高表达,并与胆管癌EMT具有相关性,可能参与了胆管癌的侵袭与转移。这为胆管癌的预防及治疗寻找新靶点提供了参考。

Objective To study the expression of Wnt2b protein and the epithelial-mesenchymal transition related markers in tissues of carcinoma of bile duct and normal bile duct to determine the clinical significance. The relationships between the expression levels and clinicopathological characteristics were analyzed, and the correlation between Wnt2b and epithelial interstitial transformation (EMT), tumor invasion and metastasis were studied. Methods A total of 60 patients with cholangiocarcinoma and 30 patients with normal bile duct tissues admitted to the Affiliated Hospital of Qingdao University from December 2008 to December 2013 were studied. The expressions of Wnt2b, E-cadherin and Vimentin protein were detected by SP immunohistochemical staining. The patients were classified according to the expressions of these proteins. Analyses were conducted on the relationships of these proteins with clinical characteristics of the patients with cholangiocarcinoma. Results The positive expression rate of Wnt2b protein in carcinoma of bile duct tissues was 90.0%, which was significantly higher than that in normal bile duct tissues (χ^2=38.1, P<0.05). The positive expression rate of Wnt2b in T3 + T4 was significantly higher than that in T1 + T2 (P<0.05). There were no correlations of the expression with patients’ age, gender, tumor location and degree of tumor differentiation (P>0.05). Patients with lymph node metastasis had a significantly higher positive expression of Vimentin than patients with no lymph node metastasis, and the loss of E-cadherin expression was increased (all P<0.05). There were no relationship of the expressions of these proteins with patients’ age, gender, tumor location and degree of tumor differentiation (P>0.05). The increased expression of Wnt2b in bile duct cancer cells was related to increase in EMT marker of the positive expression of vimentin and the loss of E-cadherin expression (both P<0.05). Conclusions Wnt2b protein overexpression in cholangiocarcinoma correlated with epithelial-mesenchymal transition related markers. The Wnt2b protein was correlated with cholangiocarcinoma occurrence, development, invasion and metastasis. Wnt2b has the potential to develop into a new therapeutic target for carcinoma of bile duct.