文章摘要

HIP1 与 AKT/GSK3β 信号通路及上皮间充质转化标志性分子在食管鳞癌组织中的表达及其相关性

作者: 1孙盈, 1夏靖华, 1王雪娇, 1文苗苗, 1张晏宁, 1张娇, 1张志培, 1李小飞
1 空军军医大学第二附属医院胸外科,西安 710038
通讯: 张志培 Email: zzpzyy@fmmu.edu.cn
李小飞 Email: lixiaofeichest@fmmu.edu.cn
DOI: 10.3978/j.issn.2095-6959.2019.03.009
基金: 空军军医大学唐都医院创新发展基金 (2016JCYJ009)。

摘要

目的:检测亨廷顿蛋白相互作用蛋白1(Huntingtin interacting protein 1,HIP1),AKT/GSK3β信号通路及上皮间充质转化(epithelial-mesenchymal transition,EMT)关键分子蛋白在食管鳞癌中的表达,探讨HIP1表达与AKT/GSK3β信号通路及EMT之间的相关性,为进一步研究HIP1在食管鳞癌中的作用及其机制提供依据。方法:采用免疫组织化学法检测85例食管鳞癌组织及其对应癌旁组织样本中HIP1,p-GSK3β,EMT标志性分子E-cadherin及Vimentin的表达,并统计分析几者在临床病理特征中的表达差异及HIP1与p-GSK3β,E-cadherin,Vimentin表达之间的相关性。采用荧光定量PCR(RT-qPCR)法检测HIP1,GSK3β,E-cadherin及Vimentin基因在食管癌及其癌旁组织中的表达。结果:HIP1,p-GSK3β,E-cadherin及Vimentin在食管鳞癌组织中的阳性表达率分别为91.8%(78/85),82.35%(70/85),15.29%(13/85),80%(68/85),分别与癌旁组织中的表达差异有统计学意义(P<0.001)。HIP1,p-GSK3β,E-cadherin在不同病理分级组间的表达差异有统计学意义(P<0.05),而Vimentin在临床病理特征各组组间的表达差异均无统计学意义(P>0.05)。相关性结果显示,HIP1与p-GSK3β及Vimentin在总的食管鳞癌中的表达均呈显著正相关(P<0.05),HIP1与E-cadherin在总的食管鳞癌中的表达呈显著负相关(P<0.01)。RT-qPCR结果发现,HIP1,GSK3β及Vimentin基因在食管鳞癌中的表达均高于其对应的癌旁组织,而E-cadherin基因在食管鳞癌中的表达低于其对应的癌旁组织。结论:HIP1表达与p-GSK3β,E-cadherin及Vimentin间存在相关性,提示HIP1可能促进食管鳞癌组织中GSK3β及Vimentin的表达,抑制E-cadherin的表达。
关键词: 亨廷顿蛋白相互作用蛋白1;食管癌;上皮间充质转化;信号通路;癌变

Expression and correlation of HIP1 with AKT/GSK3β signal pathway and EMT signaling molecules in esophageal squamous cell carcinoma tissues

Authors: 1SUN Ying, 1XIA Jinghua, 1WANG Xuejiao, 1WEN Miaomiao, 1ZHANG Yanning, 1ZHANG Jiao, 1ZHANG Zhipei, 1LI Xiaofei
1 Department of Thoracic Surgery, Second Affiliated Hospital of Air Force Medical University, Xi’an 710038, China

CorrespondingAuthor: ZHANG Zhipei Email: zzpzyy@fmmu.edu.cn

DOI: 10.3978/j.issn.2095-6959.2019.03.009

Foundation: This work was supported by the Air Force Medical University Tangdu Hospital Innovation and Development Foundation, China (2016JCYJ009).

Abstract

Objective: To explore the effect and mechanism of HIP1 in esophageal squamous cell carcinoma (ESCC) carcinogenesis through exam the expression and correlation research of HIP1 with AKT/GSK3β signal pathway and epithelial-mesenchymal transition (EMT) in ESCC. Methods: In this study, HIP1, p-GSK3β, E-cadherin, Vimentin expressions were assessed using immunohistochemistry (IHC) in 85 ESCC and adjacent ESCC tissues and the correlation research of HIP1 with p-GSK3β, E-cadherin, Vimentin were analyzed. RT-qPCR was used to detect the gene expression of HIP1, GSK3β, E-cadherin and Vimentin in ESCC and adjacent ESCC tissues. Results: The expression rate of HIP1, p-GSK3β, E-cadherin, Vimentin in ESCC (91.8%, 82.35%, 15.29%, 80%) showed extremely significance compared with adjacent ESCC tissues (P<0.001). HIP1, p-GSK3β, E-cadherin expression was significantly associated with pathological grades (P<0.05), and there was no significance between Vimentin expression with clinicopathologic features (P>0.05). The correlation research showed that there were significant positive correlations between HIP1 and p-GSK3β, as well as Vimentin (P<0.05), and there was significant negative correlation between HIP1 and E-cadherin (P<0.01). RT-qPCR results showed that compared with adjacent ESCC tissues, HIP1, GSK3β and Vimentin gene were higher expressed in ESCC tissues, but E-cadherin gene was lower expressed in ESCC tissues. Conclusion: HIP1 maybe promote p-GSK3β and Vimentin expression and inhibit E-cadherin expression.
Keywords: Huntingtin interacting protein 1; esophageal squamous cell carcinoma; epithelial-mesenchymal transition; signal pathway; carcinogenesis