摘要
目的探讨人表皮生长因子受体2(Her2)和Split多毛增强子1(Hes1)在Correa级联反应慢性浅表性胃炎(CSG)-肠上皮化生(IM)-肠型胃癌(IGC)中的表达及IGC发病的分子机制。方法运用免疫组织化学(IHC)法检测30例CSG、41例IM以及135例IGC标本中Her2及Hes1蛋白的表达水平;运用Western blot检测人胃黏膜上皮细胞GES-1、人IGC细胞株NCl-N87及MKN74中蛋白的表达水平;观察CSG胃腺体中Her2及Hes1蛋白的分布位置,比较它们在胃腺体小凹、峡部、颈部、基底部、IM、IGC及不同细胞株中表达不同。多组间均值比较采用单因素方差分析,事后两两比较采用LSD法进行分析。两组中位数比较采用Mann-Whitney U检验,多组中位数比较采用Kruskal-Wallis(KW)H检验,并采用Bonferroni校正,相关性统计采用Spearman秩分析。结果IHC法检测结果显示,与小凹比较,峡部、颈部、基底部、IM及IGC的Her2(+++)表达降低[1(3.3%),0(0.0%),0(0.0%),4(9.8%),10(7.4%)比14(46.7%);P均<0.05];峡部与IM中Her2的表达居中,均高于颈部、基底部及IGC(P<0.001);颈部、基底部及IGC中Her2的表达最弱,三者之间比较差异无统计学意义(P>0.05)。与小凹比较,峡部、颈部、基底部、IM及IGC的Hes1表达(++)升高[9(30.0%),4(13.3%),21(51.2%),39(28.9%)比0(0.0%);P均<0.05];基底部中Hes1的表达最强,高于峡部、颈部、IM及IGC(P<0.01);IM与IGC中Hes1的表达分别强于峡部与颈部(P<0.05);IM与IGC、峡部与颈部中Hes1的表达差异无统计学意义(P>0.05)。Her2/Hes1在小凹、峡部、颈部、基底部、IM及IGC中的表达均呈负相关(r_(s)=-0.794,r_(s)=-0.300,r_(s)=-0.834,r_(s)=-0.921,r_(s)=-0.258,r_(s)=-0.528,P均<0.05)。Western blot检测结果显示,Her2/Hes1在GES-1、NCl-N87及MKN74中的表达均呈负相关(r_(s)=-0.776,r_(s)=-0.671,r_(s)=-0.614,P均<0.05)。结论Correa级联反应CSG到IM最终发展至IGC进程中,Her2与Hes1蛋白呈负相关表达;与小凹比较,Her2随病程进展表达逐渐减少,Hes1的表达适度上调。
Objective To investigate the expression of human epidermal growth factor receptor 2(Her2)and Split hairy enhancer 1(Hes1)among chronic superficial gastritis(CSG)-intestinal metaplasia(IM)-intestinal type gastric cancer(IGC)in Correa cascade,exploring the molecular mechanism of IGC pathogenesis.Methods Immunohistochemistry(IHC)was used to detect the expression levels of Her2 and Hes1 proteins in 30 CSG,41 IM,and 135 IGC specimens.Western blot was used to detect the expression levels of these two proteins in the gastric epithelial cells GES-1,human IGC cell lines NCl-N87,and MKN74.The spatial location information of Her2 and Hes1 proteins in CSG gastric gland was observed,their different expressions in the gastric pit,isthmus,neck,basal regions,IM,IGC,and different cell lines were compared One-way analysis of variance was used for comparison of means among multiple groups,and LSD t test was used for post hoc pairwise comparisons.Mann-Whitney U test was used to compare the medians of two groups,and Kruskal-Wallis(KW)H test was used to compare the medians of multiple groups with Bonferroni correction.Spearman rank analysis was used for correlation statistics.Results IHC results showed that the expression of Her2(+++)in the isthmus,neck,basal region,IM and IGC was lower than that in the pit[1(3.3%),0(0.0%),0(0.0%),4(9.8%),10(7.4%)vs 14(46.7%);all P<0.05].The expressions of Her2 in the isthmus and IM was moderate,both higher than that in the neck,base,and IGC(P<0.001).The expression of Her2 was the weakest in the neck,base,and IGC,and there was no significant difference among them(P>0.05).The expression of Hes1(++)in the isthmus,neck,basal region,IM and IGC was higher than that in the pit[9(30.0%),4(13.3%),21(51.2%),39(28.9%)比0(0.0%);all P<0.05].The expression of Hes1 is strongest in the basal region,higher than that in the isthmus,neck,IM and IGC(P<0.001).The expression of Hes1 in IM and IGC was stronger than that in the isthmus and neck,respectively(P<0.05).There was no significant difference of the expression of Hes1 between IM and IGC,and between isthmus and neck(P>0.05).The expression of Her2/Hes1 was significantly negatively correlated in the pit,isthmus,neck,basal region,IM,and IGC(r_(s)=-0.794,r_(s)=-0.300,r_(s)=-0.834,r_(s)=-0.921,r_(s)=-0.258,r_(s)=-0.528,all P<0.05).Western blot results revealed that the expression of Her2/Hes1 was significantly negatively correlated in GES-1,NCl-N87 and MKN74(r_(s)=-0.776,r_(s)=-0.671,r_(s)=-0.614,all P<0.05).Conclusions In the Correa cascade from CSG to IM,eventually progressing to IGC,Her2 and Hes1 proteins exhibited a negative correlation.Compared with the pit,Her2 expression was gradually decreased with the progression of the disease,while Hes1 expression was moderately upregulated.
作者
刘先勇
秦东梅
张若梅
李俊娇
孟春芹
邬明歆
王玉红
赵新鲜
徐瑞联
洪文文
马玲
仇玮
周宇
Xianyong Liu;Dongmei Qin;Ruomei Zhang;Junjiao Li;Chunqin Meng;Mingxin Wu;Yuhong Wang;Xinxian Zhao;Ruilian Xv;Wenwen Hong;Ling Ma;Wei Qiu;Yu Zhou(Integrated TCM&Western Medicine Department,Jiangning Hospital,Nanjing Medical University,Nanjing 211100,China;Department of Pathology,Jiangning Hospital,Nanjing Medical University,Nanjing 211100,China;Central Laboratory,Jiangning Hospital,Nanjing Medical University,Nanjing 211100,China)
出处
《中华细胞与干细胞杂志(电子版)》
2024年第6期321-327,共7页
Chinese Journal of Cell and Stem Cell(Electronic Edition)
基金
南京市卫生科技发展专项资金项目(YKK22225)。
