MMP-2、TIMP-2在食管鳞状细胞癌的表达与临床意义
Expression of MMP-2 and TIMP-2 in esophageal squamous cell carcinoma and its clinical significance correlations
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摘要: 目的：探讨基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶抑制剂-2（TIMP-2）在食管鳞状细胞癌（ESCC）中的表达与术后复发或转移和预后之间的关系。方法：采用组织芯片技术，用免疫组织化学法检测ESCC术后存活5年以上且无复发转移组（A组）和术后在1年内发生复发转移死亡组（B组）肿瘤组织细胞中的MMP-2、TIMP-2表达情况。结果：MMP-2、TIMP-2在正常食管鳞状上皮中不表达或少量表达，在ESCC组织中有不同程度的表达，但MMP-2和TIMP-2在B组的表达水平均显著高于A组（P<0.01）。MMP-2表达与肿瘤分化程度和有无淋巴结转移均有相关关系（P<0.05和P<0.01）；TIMP-2表达与分化程度和有无淋巴结转移率亦均有相关关系（P<0.01和P<0.05）。TIMP-2表达与MMP2表达呈正相关关系（P<0.01）。结论：MMP-2、TIMP-2 表达在食管癌组织中高表达，其表达情况与食管癌术后发生复发转移有明显相关性，联合检测 MMP-2、TIMP-2表达对预测ESCC术后发生复发转移和预后有重要价值。
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关键词:
- 食管肿瘤 /
- 基质金属蛋白酶-2 /
- 基质金属蛋白酶抑制剂-2 /
- 复发 /
- 转移
Abstract: Objective:To investigate the expressions of the matrix metalloproteinase-2(MMP-2) and matrix metalloproteinase inhibitor-2(TIMP-2) in esophageal squamous cell carcinoma(ESCC),and its correlations with the recurrence,metastasis and prognosis of tumor.Methods:The expressions of MMP-2 and TIMP-2 in tumor tissue of the postoperative patients with ESCC were detected using the immunohistochemistry with Tissue Chip technique.The patients without recurrence and metastasis survived for over 5 years(group A),the patients with recurrence and metastasis died within 1 year(group B).Results:The squamous epithelium of the normal esophagus did not express or expressed little MMP-2 and TIMP-2.The expressions of MMP-2 and TIMP-2 in ESCC tissue were identified,but the expression levels of MMP-2 and TIMP-2 in group B were significantly higher than those in group A(P< 0.01).The expression levels of MMP-2 and TIMP-2 were correlated with the tumor differentiation and lymph node metastasis(P<0.05 and P<0.01).The expression level of TIMP-2 was positively correlated with the MMP-2(P<0.01).Conclusions:MMP-2 and TIMP-2 are overexpressed in esophageal carcinoma tissue,and which are significantly correlated with the recurrence or metastasis of tumor after esophagectomy.The combined detection of MMP-2 and TIMP-2 has important value in predicting the recurrence or metastasis of tumor after operation of ESCC. -
[1] 郭文忠,冉宇靓,王贵齐,等.VEGF 和 MMP-9在食管癌中的表达及低氧调节[J].中华肿瘤杂志,2002,24(1):44. [2] HERSZÉNYI L,HRITZ I,LAKATOS G,et al.The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer[J].Int J Mol Sci,2012,13(10):13240. [3] WOLF K,TE LINDERT M,KRAUSE M,et al.Physical limits of cell migration:control by ECM space and nuclear deformation and tuning by proteolysis and traction force[J].J Cell Biol,2013,201(7):1069. [4] BOURBOULIA D,STETLER-STEVENSON WG.Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs):Positive and negative regulators in tumor cell adhesion[J].Semin Cancer Biol,2010,20(3):161. [5] ITOH Y.Membrane-type matrix metalloproteinases:Their functions and regulations[J].Matrix Biol,2015,44-46:207. [6] 王小军,杨文平.bFGF、MMPs和TIMPs在肿瘤临床研究中的进展[J].中国现代医药杂志,2012,14(2):126. [7] AUGOFF K,HRYNIEWICZ-JANKOWSKA A,TABOLA R,et al.Up-regulated expression and activation of invadopodia-associated proteases in esophageal squamous cell carcinoma (ESCC)[J].Cancer Research,2013,73(8 Suppl):5056. [8] JING S,WANG Y,CHEN L Q,et al.Hypoxia suppresses E-cadherin and enhances matrix metalloproteinase-2 expression favoring esophageal carcinoma migration and invasion via hypoxia inducible factor-1 α activation[J].Dis Esophagus,2013,26(1):75. [9] PARK MK,JO SH,LEE HJ,et al.Novel suppressive effects of cardamonin on the activity and expression of transglutaminase-2 lead to blocking the migration and invasion of cancer cells[J].Life Sci,2013,92(2):154. [10] LI X,YANG Z,SONG W,et al.Overexpression of Bmi-1 contributes to the invasion and metastasis of hepatocellular carcinoma by increasing the expression of matrix metalloproteinase (MMP)2,MMP-9 and vascular endothelial growth factor via the PTEN/PI3K/Akt pathway[J].Int J Oncol,2013,43(3):793. [11] REMILLARD TC,BRATSLAVSKY G,JENSEN-TAUBMAN S,et al.Molecular mechanisms of tissue inhibitor of metalloproteinase 2 in the tumor microenvironment[J].Mol Cellular Ther,2014,2:17. [12] BREW K,NAGASE H.The tissue inhibitors of metalloproteinases (TIMPs):an ancient family with structural and functional diversity[J].Biochim Biophys Acta,2010,1803(1):55. [13] DANIELE A,DIVELLA R,QUARANTA M,et al.Clinical and prognostic role of circulating MMP-2 and its inhibitor TIMP-2 in HCC patients prior to and after trans-hepatic arterial chemo-embolization[J].Clin Biochem,2014,47(3):184. [14] BREW K,DINAKARPANDIAN D,NAGASE H.Tisue inhibitor of metallop roteinases:evolution,structure,and function[J].Biochim Biophys Acta,2000,1477(1/2):267. [15] WANG YZ,WU KP,WU AB,et al.MMP-14 overexpression correlates with poor prognosis in non-small cell lung cancer[J].Tumor Biol,2014,35(10):9815. [16] 朱自江,陈学忠,牛荣,等.食管癌患者术后肿瘤复发和转移的危险因素[J].中国胸心血管外科临床杂志,2011,18(6):521. -
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