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

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。

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.