FOXC2在肝外胆管细胞癌中的表达及其对肿瘤侵袭迁移和上皮间质转化的作用  

High expression of FOXC2 promotes invasion and migration and epithelial mesenchymal transformation of extrahepatic cholangiocarcinoma

作　　者：晋云 胡苹苹 翟建新 李星逾[1,3] 孙志为 杨超[1,3] 陈晓波 王峻峰[1,2,3] JIN Yun;HU Ping-ping;ZHAI Jian-xin;LI Xing-yu;SUN Zhi-wei;YANG Chao;CHEN Xiao-bo;WANG Jun-feng(Department of Hepatobiliary Surgery,The First People’s Hospital of YunnanProvince(Kunming 650000,China;Department of Digital Medical Research Center,The First People’s Hospital of YunnanProvince(Kunming 650000,China;The Affiliated Hospital of Kunming University of Science and Technology(Kunming 65000,China)

机构地区：[1]云南省第一人民医院肝胆胰外科,云南昆明650000 [2]云南省第一人民医院数字医学研究中心,云南昆明650000 [3]昆明理工大学附属医院肝胆胰外科,云南昆明650000

出　　处：《中国现代普通外科进展》2020年第6期431-438,共8页Chinese Journal of Current Advances in General Surgery

基　　金：国家自然科学基金委员会-地区项目(81960514);昆医联合专项-重点项目[2019FE001(-010)];云南省高层次卫生计生技术人才-医学学科带头人项目(D-2017018);云南省中青年学术和技术带头人-后备人才项目。

摘　　要：目的:检测FOXC2在肝外胆管细胞癌(EHCC)中表达的临床意义,并初步探讨FOXC2在体外对EHCC肿瘤细胞增殖、侵袭迁移和上皮间质转化的作用。方法:免疫组织化学法检测FOXC2在EHCC组织和正常胆管组织中的表达;qRT-PCR检测FOXC2 m RNA在EHCC组织和正常胆管组织中的表达;分析FOXC2表达水平与患者临床病理因素和预后的关系。选择FOXC2高表达的HuCCT1细胞进行转染敲降FOXC2,CCK-8实验检测细胞增殖活力;Transwell实验检测细胞的迁移和侵袭能力;Westernblot检测上皮间质转化蛋白E-cadherin、N-cadherin、Vimentin和MMP-2的表达。结果:免疫组化结果表明,77例EHCC样本中68例(88.3%)FOXC2表达阳性。qRT-PCR检测结果表明FOXC2mRNA在EHCC组织的表达水平显著高于正常胆管上皮组织。FOXC2表达水平与EHCC患者肿瘤组织分化、临床病理分级、淋巴侵犯等相关;进一步分析发现,FOXC2高表达组患者预后较差,且FOXC2高表达是影响EHCC患者临床预后的独立危险因素。体外实验结果显示,敲降FOXC2显著降低HuCCT1细胞侵袭和迁移能力,但不改变细胞增殖活力;显著降低EMT蛋白N-cadherin、Vimentin和MMP-2的表达,促进E-cadherin的表达。结论:FOXC2在EHCC组织中的高表达促进肿瘤进展并与患者不良预后相关,可能与FOXC2促进EHCC癌细胞的侵袭、迁移和上皮间质转化有关。Objective: To explore the clinical significance of FOXC2 expression in extrahepatic cholangiocarcinoma(EHCC), and investigate the effect of FOXC2 on proliferation, invasion, migration and epithelial-mesenchymal transformationof EHCC cancer cells in vitro.Methods: The expression of FOXC2 in EHCC and normal bile duct tissues were detected by immunohistochemistry. The expression of FOXC2 m RNA in EHCC and normal bile duct tissues were measured by qRT-PCR. The relationship between FOXC2 expression level and pathological indicators, survival and prognosis of EHCC patients was further analyzed.The proliferation activity of EHCC cells was tested by CCK-8 assay. Transwell assay was used to evaluate the migration and invasion of EHCC cells. Westernblot was used to detect the expression of E-cadherin, N-cadherin, Vimentin and MMP-2. Results: The immunohistochemical results showed that 68 of the 77 EHCC samples were FOXC2 positive(88.3%). The results of qRT-PCR indicated that the expression of FOXC2 m RAN in EHCC cancer tissues was significantly higher than that in normal cholangiocarcinoma tissues. The analysis of clinicopathological indicators found that the expression level of FOXC2 was correlated with low differentiation, high clinicopathological grade and lymphatic invasion of EHCC patients.Further analysis revealed that patients with high FOXC2 expression had poor prognosis, and that high FOXC2 expression was an independent risk factor affecting the clinical prognosis of EHCC patients.In vitro experiments,FOXC2 knockdown significantly reduced the invasion and migration of HuCCT1 cells, but did not change the proliferation of HuCCT1 cells.In addition, FOXC2 knockdown significantly reduced the expression of EMT proteins N-cadherin, Vimentin and MPP-2, and promoted the expression of E-cadherin. Conclusion: Clinically, the high expression level of FOXC2 in EHCC promotes cancer progression and is associated with poor prognosis. Functionally, FOXC2 promotes invasion, migration, and epithelial mesenchymal transformation in E

关 键 词：肝外胆管细胞癌 叉头框蛋白C2 侵袭转移 上皮-间质转化 

分 类 号：R735.8[医药卫生—肿瘤]