Significance of P-cadherin overexpression and possible mechanism of its regulation in intrahepatic cholangiocarcinoma and pancreatic cancer.
Significance of P-cadherin overexpression and possible mechanism of its regulation in intrahepatic cholangiocarcinoma and pancreatic cancer.
复制标题
p-钙粘蛋白过表达的重要性及其在肝内胆管癌和胰腺癌中调节的可能机制。
DOI：
10.1111/cas.12732
复制
发表时间：
2015-09
期刊：
影响因子：
5.7
通讯作者：
Baba H
中科院分区：
文献类型：
--
作者：
Sakamoto K;Imai K;Higashi T;Taki K;Nakagawa S;Okabe H;Nitta H;Hayashi H;Chikamoto A;Ishiko T;Beppu T;Baba H
很明显，经典钙粘蛋白之一P-钙粘蛋白与多种类型癌症的恶性行为有关。本研究旨在探讨P-cadherin在肝内胆管细胞癌（ICC）和胰腺癌中的表达及其临床病理和预后价值。此外，我们研究了P-cadherin在这些癌细胞中的功能作用，通过敲低和过表达在体外，并通过分析P-cadherin的表达和其启动子甲基化状态之间的相关性。免疫组化结果显示，59例ICC中30例（51%）和73例胰腺癌中36例（49%）P-cadherin阳性，主要分布于肿瘤细胞膜上。P-cadherin表达与反映肿瘤行为的几个临床病理因素显著相关，通过多变量分析，P-cadherin表达被确定为ICC（相对风险[RR] 2.93，P = 0.04）和胰腺癌（RR 2.68，P = 0.005）患者无病生存的独立不良预后因素。通过siRNA下调P-cadherin抑制迁移和侵袭，P-cadherin过表达在ICC和胰腺癌细胞中诱导相反的作用，而对细胞增殖没有任何影响。P-cadherin在细胞系和癌组织中的表达与其启动子甲基化状态有关。综上所述，P-cadherin的过度表达可能作为一个有用的生物标志物的侵袭性表型和预后不良; P-cadherin的表达被发现是由其启动子甲基化调控。这些结果表明，P-cadherin代表了一种新的治疗ICC和胰腺癌的治疗靶点。
It has become evident that P-cadherin, one of the classical cadherins, contributes to the malignant behavior of several types of cancer. In this study, we analyzed the expression of P-cadherin and its clinicopathological and prognostic values in intrahepatic cholangiocarcinoma (ICC) and pancreatic cancer. Furthermore, we investigated the functional role of P-cadherin in these cancer cells by knockdown and overexpression in vitro and by analyzing the correlation between the P-cadherin expression and its promoter methylation status. Thirty of 59 ICC cases (51%) and 36 of 73 pancreatic cancer cases (49%) stained positive for P-cadherin with mainly membranous distribution in tumor cells by immunohistochemistry. P-cadherin expression was significantly correlated with several clinicopathological factors, which reflect tumor behavior, and was identified as an independent adverse prognostic factor for disease-free survival in patients with ICC (relative risk [RR] 2.93, P = 0.04) and pancreatic cancer (RR 2.68, P = 0.005) via multivariate analyses. P-cadherin downregulation by siRNA suppressed migration and invasion, and P-cadherin overexpression induced the opposite effects in both ICC and pancreatic cancer cells, without any effects on cell proliferation. P-cadherin expression was related to its promoter methylation status in both cell lines and cancer tissues. In summary, P-cadherin overexpression may serve as a useful biomarker of invasive phenotype and poor prognosis; P-cadherin expression was found to be regulated by its promoter methylation. These results suggest that P-cadherin represents a novel therapeutic target for the treatment of ICC and pancreatic cancer.