Claudin-4和MMP-9在胃癌中的表达和临床意义
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摘要
紧密连接(tight junction, TJ)是重要的相邻细胞间的膜连接复合体。Claudin是决定TJ功能最重要的紧密连接骨架蛋白,其中Claudin-4与胃癌关系密切。基质金属蛋白酶-9(MMP-9)作为基质金属蛋白酶的一种,能降解基底膜和细胞外基质成分,从而促进肿瘤的浸润、转移及间质血管新生。目前国内外关于Claudin-4、MMP-9与胃癌临床病理参数的关系以及Claudin-4和MMP-9二者间相互关系的研究很少。
本研究共收集福建医科大学附属厦门第一医院,厦门市肿瘤中心肿瘤外科2007年9月至2009年9月部分胃癌手术标本,共68例。经石蜡切片,HE染色,采用免疫组织化学染色方法检测癌组织中Claudin-4、MMP-9蛋白表达。其中还收集20例新鲜标本,每例标本均包括胃癌组织和距癌边缘5㎝胃正常上皮组织,分别采用免疫组织化学染色和实时定量PCR检测Claudin-4、MMP-9蛋白和mRNA在胃癌组织和胃正常上皮组织中的表达。分析胃癌组织中Claudin-4和MMP-9的表达与胃癌临床病理特点的关系以及两者之间的相互关系。
结果显示,Claudin-4在肠型胃癌和BorrmannⅠ型和Ⅱ型胃癌组织中的表达分别显著高于弥漫型胃癌和BorrmannⅢ型与Ⅳ型胃癌组织中的表达(P <0.05);Claudin-4的表达与胃癌分化程度相关,胃癌分化程度越差,Claudin-4表达越低(P <0.05);相反,MMP-9在肠型胃癌和BorrmannⅠ型和Ⅱ型胃癌组织中的表达分别显著低于在弥漫型胃癌和BorrmannⅢ型与Ⅳ型胃癌组织中的表达(P <0.05);MMP-9的表达与胃癌分化相关,胃癌分化越差,MMP-9表达越高(P <0.05);胃癌组织中Claudin-4和MMP-9蛋白的表达显著高于正常胃上皮组织中的表达(P <0.05);Claudin-4和MMP-9的表达明显相关(P >0.05)。Claudin-4和MMP-9与胃癌的发生、发展及胃癌的生物学行为密切相关,它们可能成为预测胃癌预后的指标。
Tight junctions(TJ) are important intercellular junctional complexes and Claudins are the most important tight junction scaffolding proteins which determine the functions of TJ. Among them, Claudin-4 is closely related with gastric cancer. As a matrix metalloproteinase(MMPs), matrix metalloproteinase-9 (MMP-9) degrades basement membranes and extracellular matrix components, thereby promoting tumor invasion, metastasis and interstitial angiogenesis. There is few literature about the relationship between the expression of Claudin-4,MMP-9 and the clinicopathological significance of gastric cancer and the relationship between Claudin-4 and MMP-9 in gastric cancer.
To discuss the expression and clinicopathological significance of Claudin-4 and MMP-9 as well as their correlation in human gastric cancer, 68 tissue specimens of gastric cancer were collected from September 2007 to September 2009, Of which 20 cases made into paraffin sections and fresh frozen specimens were stored. Then, expression of Claudin-4,MMP-9 proteins and mRNA were detected in gastric cancer tissues and normal gastric tissues by immunohistochemical staining and real time quantitative PCR respectively. Claudin-4 and MMP-9 proteins in gastric cancer tissues by immunohistochemistry were detected in the left 48 tissue specimens which were only made into paraffin sections .The relationship between the expression of claudin-4 and MMP-9 and clinicopathological parameters were analysed.
Results shows that the expression of Claudin-4 in gastric cancer tissues of intestinal-type and Borrmann type I and II was significantly higher than that in diffuse type and Borrmann type III and IV respectively(P <0.05),Claudin-4 expression was correlated with cell differentiation of gastric cancer, the worse differentiation of gastric cancer, the lower expression of Claudin-4(P <0.05).On the contrary,MMP-9 expression in gastric cancer tissues of intestinal-type and Borrmann type I and II was significantly lower than that in diffuse type and Borrmann type III and IV respectively(P <0.05);MMP-9 expression was correlated with cell differentiation of gastric cancer, the worse differentiation of gastric cancer, the higher expression of MMP-9(P <0.05) . The expression of Claudin-4,MMP-9 in gastric cancer tissues was significantly higher than normal gastric foveolar epithelial tissues(P <0.05), and the correlation between expression of Claudin-4 and MMP-9 was also found(P <0.05). The expression of Claudin-4 and MMP-9 are correlated with the incidence and the biological behavior of gastric cancer and could be used to predict the biological behavior of gastric cancer.
本研究共收集福建医科大学附属厦门第一医院,厦门市肿瘤中心肿瘤外科2007年9月至2009年9月部分胃癌手术标本,共68例。经石蜡切片,HE染色,采用免疫组织化学染色方法检测癌组织中Claudin-4、MMP-9蛋白表达。其中还收集20例新鲜标本,每例标本均包括胃癌组织和距癌边缘5㎝胃正常上皮组织,分别采用免疫组织化学染色和实时定量PCR检测Claudin-4、MMP-9蛋白和mRNA在胃癌组织和胃正常上皮组织中的表达。分析胃癌组织中Claudin-4和MMP-9的表达与胃癌临床病理特点的关系以及两者之间的相互关系。
结果显示,Claudin-4在肠型胃癌和BorrmannⅠ型和Ⅱ型胃癌组织中的表达分别显著高于弥漫型胃癌和BorrmannⅢ型与Ⅳ型胃癌组织中的表达(P <0.05);Claudin-4的表达与胃癌分化程度相关,胃癌分化程度越差,Claudin-4表达越低(P <0.05);相反,MMP-9在肠型胃癌和BorrmannⅠ型和Ⅱ型胃癌组织中的表达分别显著低于在弥漫型胃癌和BorrmannⅢ型与Ⅳ型胃癌组织中的表达(P <0.05);MMP-9的表达与胃癌分化相关,胃癌分化越差,MMP-9表达越高(P <0.05);胃癌组织中Claudin-4和MMP-9蛋白的表达显著高于正常胃上皮组织中的表达(P <0.05);Claudin-4和MMP-9的表达明显相关(P >0.05)。Claudin-4和MMP-9与胃癌的发生、发展及胃癌的生物学行为密切相关,它们可能成为预测胃癌预后的指标。
Tight junctions(TJ) are important intercellular junctional complexes and Claudins are the most important tight junction scaffolding proteins which determine the functions of TJ. Among them, Claudin-4 is closely related with gastric cancer. As a matrix metalloproteinase(MMPs), matrix metalloproteinase-9 (MMP-9) degrades basement membranes and extracellular matrix components, thereby promoting tumor invasion, metastasis and interstitial angiogenesis. There is few literature about the relationship between the expression of Claudin-4,MMP-9 and the clinicopathological significance of gastric cancer and the relationship between Claudin-4 and MMP-9 in gastric cancer.
To discuss the expression and clinicopathological significance of Claudin-4 and MMP-9 as well as their correlation in human gastric cancer, 68 tissue specimens of gastric cancer were collected from September 2007 to September 2009, Of which 20 cases made into paraffin sections and fresh frozen specimens were stored. Then, expression of Claudin-4,MMP-9 proteins and mRNA were detected in gastric cancer tissues and normal gastric tissues by immunohistochemical staining and real time quantitative PCR respectively. Claudin-4 and MMP-9 proteins in gastric cancer tissues by immunohistochemistry were detected in the left 48 tissue specimens which were only made into paraffin sections .The relationship between the expression of claudin-4 and MMP-9 and clinicopathological parameters were analysed.
Results shows that the expression of Claudin-4 in gastric cancer tissues of intestinal-type and Borrmann type I and II was significantly higher than that in diffuse type and Borrmann type III and IV respectively(P <0.05),Claudin-4 expression was correlated with cell differentiation of gastric cancer, the worse differentiation of gastric cancer, the lower expression of Claudin-4(P <0.05).On the contrary,MMP-9 expression in gastric cancer tissues of intestinal-type and Borrmann type I and II was significantly lower than that in diffuse type and Borrmann type III and IV respectively(P <0.05);MMP-9 expression was correlated with cell differentiation of gastric cancer, the worse differentiation of gastric cancer, the higher expression of MMP-9(P <0.05) . The expression of Claudin-4,MMP-9 in gastric cancer tissues was significantly higher than normal gastric foveolar epithelial tissues(P <0.05), and the correlation between expression of Claudin-4 and MMP-9 was also found(P <0.05). The expression of Claudin-4 and MMP-9 are correlated with the incidence and the biological behavior of gastric cancer and could be used to predict the biological behavior of gastric cancer.
引文
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35 Hisashi Miyamori, Takahisa Takino,Yuko Kobayashi, et al. Claudin promotes activity of pro-matrix metalloproteinase-2 mediated by membrane-type matrix metallopreinases.J.Biol.Chem,2001,276(30):28204-28211.
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