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肺癌组织中MMP-9及TIMP-1的表达与转移、预后相关性研究

Expressions of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 and their correlation with metastasis and prognosis in lung cancer

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【作者】 梁君刘铭球谢梅刘绚

【Author】 LIANG Jun, LIU Mingqiu, XIE Mei, LIU Xuan. Department of Nuclear Medicine, Wuhan University People Hospital, Wuhan, Hubei 430060, P.R.China

【机构】 武汉大学人民医院核医学科武汉大学人民医院病理教研室武汉大学人民医院病理教研室 430060武汉430060武汉

【摘要】 目的 探讨MMP 9及其抑制剂TIMP 1在人肺癌中的表达及其与肺癌转移、预后的相关性 ,分析肺癌发生、发展、侵袭和转移的机制。方法 应用免疫组化S P法检测 65例肺癌、3 5例其他肺部疾患病变支气管粘膜增生及不典型增生上皮和 3 0例正常支气管粘膜上皮组织中MMP 9和TIMP 1的蛋白表达。结果 肺癌与正常、增生上皮相比 ,增生与正常上皮相比 ,MMP 9和TIMP 1阳性表达率的升高均具有显著性(P <0 .0 5 )。不同组织学类型中MMP 9的阳性表达有显著性差异 (P <0 .0 2 5 ) ;MMP 9的阳性表达与肺癌细胞分化程度负相关 (P <0 .0 5 ) ,与TNM分期正相关 (P <0 .0 2 5 )。生存期小于 2年者的MMP 9和TIMP 1阳性表达率显著高于生存期大于或等于 2年者 (P <0 .0 5 )。MMP 9阳性表达上调与肺癌转移相关 (P <0 .0 0 5 ) ,TIMP 1与转移无关。结论 MMP 9阳性表达上调可出现在癌前病变及肺癌发病的早期阶段 ,MMP 9基因激活可能是肺癌癌变的重要因素 ;MMP 9、TIMP 1在肺肿瘤浸润转移中发挥重要作用 ,其过度表达可作为评估肺癌浸润转移和预后不良的参考指标。

【Abstract】 Objective To investigate the expressions of matrix metalloproteinase 9 (MMP 9) and tissue inhibitor of metalloproteinase 1 (TIMP 1) and their correlation with metastasis and prognosis in human lung cancer. Methods Immunohistochemical S P method was used to detect the expression of MMP 9 and TIMP 1 in 65 lung cancer tissues, 35 hyperplastic and dysplastic epithelium from patients with non cancerous pulmonary diseases, and 30 normal epithelial tissues of the lung. Results The positive expression rates of MMP 9 in normal tissue, hyperplastic or dysplastic epithelium, and lung cancer tissue were 16.7%(5/30), 42.9%(15/35) and 72.3%(47/65) respectively, whereas the positive rates of TIMP 1 expression in normal tissue, hyperplastic or dysplastic epithelium, and lung cancer tissue were 6.7%(2/30), 28.6%(10/35) and 50.8%(33/65) respectively. Significant differences of the expression rates of MMP 9 and TIMP 1 were found between lung cancer and normal groups, between lung cancer and hyperplasia groups, and between hyperplasia and normal groups (P<0.05). Small cell carcinoma and adenocarcinoma had higher MMP 9 expression than squamous cell carcinoma (P<0.025). Expression rate of MMP 9 had negative relation with cell differentiation of lung cancer (P<0.05), and positive relation with TNM stage (P<0.025). Between the survival time <2 years group and ≥2 years groups, both the expressions of MMP 9 and TIMP 1 had significant difference (P< 0.05 ). The expression of MMP 9 was closely related to metastasis of lung cancer (P<0.005), but the expression of TIMP 1 was not related to metastasis. Conclusion Overexpression of MMP 9 may appear in precancerous lesion and at the early stage of lung cancer. Activation of MMP 9 gene may be an important factor for oncogenesis of the lung. MMP 9 and TIMP 1 may play important roles in lung cancer invasion and metastasis, their overexpression could act as a reference to evaluate metastasis and unfavourable prognosis of lung cancer.

【基金】 国家自然科学基金 (39870 30 5)资助
  • 【文献出处】 中国肺癌杂志 ,Chinese Journal of Lung Cancer , 编辑部邮箱 ,2003年01期
  • 【分类号】R734.2
  • 【被引频次】37
  • 【下载频次】146
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