TFF2、CLDN18、MUC5AC蛋白在胃黏膜病变过程中的表达变化及其临床意义
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摘要
背景:胃癌是我国发病率和死亡率最高的恶性肿瘤之一,胃黏膜病变过程中早期分子标记是近年胃癌研究的重点。目的:探讨三叶因子2(TFF2)、闭合蛋白18(CLDN18)和黏蛋白5AC(MUC5AC)在不同胃黏膜病变中的表达情况及其临床意义。方法:选取2008年12月-2009年5月内蒙古自治区人民医院的胃镜活检和手术标本71例,其中正常胃黏膜组织20例,肠化生组织20例,异型增生组织11例,胃癌组织20例,采用免疫组化SP法检测TFF2、CLDN18和MUC5AC蛋白表达情况。结果:正常胃黏膜组织中TFF2、CLDN18和MUC5AC蛋白均为阳性表达,表达率为100%,而肠化生、异型增生以及胃癌组织中,三种蛋白阳性表达率依次逐渐下降,组间差异有统计学意义(P<0.01)。结论:TFF2、CLDN18和MUC5AC蛋白表达水平与胃黏膜组织恶性程度密切相关,是潜在的预测胃癌发生、发展和预后的重要生物学标记。
Background: Gastric cancer is one of the malignant tumors with highest morbidity and mortality,and the early change of molecular marker in gastric mucosal lesion is the hot spot of gastric cancer study. Aims: To investigate the expressions and clinical significance of trefoil factor 2( TFF2),claudin 18( CLDN18),mucin 5AC( MUC5AC) in gastric mucosal lesions. Methods: Gastroscopy biopsies and surgery specimens from Dec. 2008 to May 2009 at Inner Mongolia People's Hospital were collected,including 20 normal gastric mucosal tissues,20 intestinal metaplasia tissues,11 dysplasia tissues and 20 gastric cancer tissues. The protein expressions of TFF2, CLDN18, MUC5 AC were determined by immunohistochemical SP method. Results: The positive expression rates of TFF2,CLDN18 and MUC5 AC in normal gastric mucosal tissues were all 100%,and were gradually decreased in the order of intestinal metaplasia,dysplasia and gastric cancer tissue,the differences were statistically significant( P < 0. 01). Conclusions: Expressions of TFF2,CLDN18 and MUC5 AC protein are closely related to the degree of malignancy of gastric mucosal lesions,and can be considered as a potential biological marker for predicting the development and prognosis of gastric cancer.
Background: Gastric cancer is one of the malignant tumors with highest morbidity and mortality,and the early change of molecular marker in gastric mucosal lesion is the hot spot of gastric cancer study. Aims: To investigate the expressions and clinical significance of trefoil factor 2( TFF2),claudin 18( CLDN18),mucin 5AC( MUC5AC) in gastric mucosal lesions. Methods: Gastroscopy biopsies and surgery specimens from Dec. 2008 to May 2009 at Inner Mongolia People's Hospital were collected,including 20 normal gastric mucosal tissues,20 intestinal metaplasia tissues,11 dysplasia tissues and 20 gastric cancer tissues. The protein expressions of TFF2, CLDN18, MUC5 AC were determined by immunohistochemical SP method. Results: The positive expression rates of TFF2,CLDN18 and MUC5 AC in normal gastric mucosal tissues were all 100%,and were gradually decreased in the order of intestinal metaplasia,dysplasia and gastric cancer tissue,the differences were statistically significant( P < 0. 01). Conclusions: Expressions of TFF2,CLDN18 and MUC5 AC protein are closely related to the degree of malignancy of gastric mucosal lesions,and can be considered as a potential biological marker for predicting the development and prognosis of gastric cancer.
引文
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12 Tsukita S,Furuse M,Itoh M.Structural and signalling molecules come together at tight junctionsr[J].Curr Opin Cell Biol,1999,11(5):628-633.
13 Martin TA,Jiang WG.Tight junctions and their role in cancer metastasis[J].Histol Histopathol,2001,16(4):1183-1195.
14 Sanada Y,Oue N,Mitani Y,et al.Down-regulation of the claudin-18 gene,identified through serial analysis of gene expression data analysis,in gastric cancer with an intestinal phenotype[J].J Pathol,2006,208(5):633-642.
15 Imbert Y,Darling DS,Jumblatt MM,et al.MUC1 splice variants in human ocular surface tissues:possible differences between dry eye patients and normal controls[J].Exp Eye Res,2006,83(3):493-501.
16 Jia Y,Persson C,Hou L,et al.A comprehensive analysis of common genetic variation in MUC1,MUC5AC,MUC6genes and risk of stomach cancer[J].Cancer Causes Control,2010,21(2):313-321.
17 Kageyama-Yahara N,Yamamichi N,Takahashi Y,et al.Gli Regulates MUC5AC transcription in human gastrointestinal cells[J].PLo S One,2014,9(8):e106106.
18 Wang C,Wang J,Liu Y,et al.MUC5AC upstream complex repetitive region length polymorphisms are associated with susceptibility and clinical stage of gastric cancer[J].PLo S One,2014,9(6):e98327.
2 房殿春,彭志红.胃粘膜屏障功能研究概况[J].现代消化及介入诊疗,2007,12(1):48-52.
3 Shi SQ,Cai JT,Yang JM.Expression of trefoil factors 1and 2 in precancerous condition and gastric cancer[J].World J Gastroenterol,2006,12(19):3119-3122.
4 Ito T,Kojima T,Yamaguchi H,et al.Transcriptional regulation of claudin-18 via specific protein kinase C signaling pathways and modification of DNA methylation in human pancreatic cancer cells[J].J Cell Biochem,2011,112(7):1761-1772.
5 Madsen J,Nielsen O,Torne I,et al.Tissue localization of human trefoil factors 1,2,and 3[J].J Histochem Cytochem,2007,55(5):505-513.
6 穆标,刘之武,王志川,等.幽门螺杆菌感染对胃粘膜三叶因子2表达的影响[J].临床荟萃,2005,20(14):787-789.
7 Peterson AJ,Menheniott TR,O’Connor L,et al.Helicobacter pylori infection promotes methylation and silencing of trefoil factor 2,leading to gastric tumor development in mice and humans[J].Gastroenterology,2010,139(6):2005-2017.
8 Blanchard C,Durual S,Estienne M,et al.IL-4 and IL-13up-regulate intestinal trefoil factor expression requirement for STAT6 and de novo protein synthesis[J].J Immunol,2004,172(6):3775-3783.
9 Beck PL,Wong JF,Li Y,et al.Chemotherapy-and radiotherapy-induced intestinal damage is regulated by intestinal trefoil factor[J].Gastroenterology,2004,126(3):796-808.
10 Schmidt PH,Lee JR,Joshi V,et al.Identification of a metaplastic cell lineage associated with human gastric adenocarcinoma[J].Lab Invest,2009,79(6):639-646.
11 Jiang P,Yu G,Zhang Y,et al.Promoter hypermethylation and down regulation of trefoil factor 2 in human gastric cancer[J].Oncol Lett,2014,7(5):1525-1531.
12 Tsukita S,Furuse M,Itoh M.Structural and signalling molecules come together at tight junctionsr[J].Curr Opin Cell Biol,1999,11(5):628-633.
13 Martin TA,Jiang WG.Tight junctions and their role in cancer metastasis[J].Histol Histopathol,2001,16(4):1183-1195.
14 Sanada Y,Oue N,Mitani Y,et al.Down-regulation of the claudin-18 gene,identified through serial analysis of gene expression data analysis,in gastric cancer with an intestinal phenotype[J].J Pathol,2006,208(5):633-642.
15 Imbert Y,Darling DS,Jumblatt MM,et al.MUC1 splice variants in human ocular surface tissues:possible differences between dry eye patients and normal controls[J].Exp Eye Res,2006,83(3):493-501.
16 Jia Y,Persson C,Hou L,et al.A comprehensive analysis of common genetic variation in MUC1,MUC5AC,MUC6genes and risk of stomach cancer[J].Cancer Causes Control,2010,21(2):313-321.
17 Kageyama-Yahara N,Yamamichi N,Takahashi Y,et al.Gli Regulates MUC5AC transcription in human gastrointestinal cells[J].PLo S One,2014,9(8):e106106.
18 Wang C,Wang J,Liu Y,et al.MUC5AC upstream complex repetitive region length polymorphisms are associated with susceptibility and clinical stage of gastric cancer[J].PLo S One,2014,9(6):e98327.