S100A_4在肺癌中的表达及其与MMP9/TIMP1表达失衡的关系

目的:研究S100A4在人肺癌中的表达及其临床生物学意义,探讨其在肺癌的侵袭和转移中的作用及其与MMP9/TIMP1表达失衡的关系。方法:采用S-P免疫组化法检测50例肺癌及6例正常肺组织中S100A4、MMP9及TIMP1的表达水平。结果:S100A4、MMP9和TIMP1在肺癌中表达显著高于正常肺组织;非小细胞肺癌中表达明显高于小细胞肺癌(P<0.05);腺癌中表达明显高于鳞癌(P<0.05)。S100A4和MMP9表达与非小细胞肺癌临床病理特征关系密切,在有淋巴结转移组与无转移组中两者均有显著性差异(P<0.05)。在肺癌不同临床TNM分期中,S100A4和MMP9阳性表达随临床分期的升高而明显增加,各期间均有显著性差异(P<0.05)。MMP9表达与非小细胞肺癌分化程度密切相关,随分化程度的降低,MMP9阳性率升高(P<0.05);S100A4阳性率随分化程度的降低也有升高趋势,但没显著性差异。S100A4表达与肿瘤大小有密切的正相关关系,随肿瘤体积的增大,S100A4的阳性率升高(P<0.05)。S100A4与MMP9呈正相关(P<0.05);MMP9与TIMP1呈正相关关系(P<0.05)。结论:S100A4和MMP9与肺癌的侵袭和转移有密切的关系,可以作为评估肺癌病人预后的重要指标。TIMP1不是简单对MMP9的局部升高起反应。S100A4参与调节MMP9的表达,则可能为肺癌的治疗开辟一条新的途径。

Expression of fibroblast specific protein-1(S100A4), matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinases 1 (TIMP1) in human lung cancer and their clinical biological significance

Objective:To determine the expression of fibroblast specific protein-1 (S100A_4), matrix metalloproteinase 9(MMP_9) and Tissue inhibitor of metalloproteinases 1(TIMP_1) in human lung cancer, and to investigate the possible roles of S100A_4, MMP_9 and TIMP_1 in the infiltration and metastasis of lung cancer.Methods:Immunohistochemical S-P method was used to detect the expression of S100A_4, MMP_9 and TIMP_1 in 50 lung cancer tissues and 6 normal lung tissues.Results: The expression of S100A_4, MMP_9 and TIMP_1 were up-regulated in lung cancer tissues. Significant differences of the expression rates of S100A_4, MMP_9 and TIMP_1 were found between lung cancer and normal groups (P<0.05), between non-small cell lung cancer and small cell lung cancer(P<0.05) and between adenocarcinoma and squamous cell carcinoma(P<0.05). The expression of S100A_4 and MMP_9 was closely related to clinicopathological characteristics of non-small cell lung cancer; lymph node metastasis groups had higher S100A_4 and MMP_9 expressions than without lymph node metastasis groups(P<0.05); In TNM stage, the positive expression of S100A_4 and MMP_9 increased remarkably fromⅠto Ⅱ, then to Ⅲ+Ⅳ (P<0.05); Expression rate of MMP_9 had negative relation with cell differentiation (P<0.05) and S100A_4 had positive relation with tumor volume (P<0.05) in non-small cell lung cancer. In lung cancer tissues, there was obvious positive correlation between S100A_4 and MMP_9, and between MMP_9 and TIMP_1. Conclusion:S100A_4 and MMP_9 may play important roles in lung cancer invasion and metastasis; their over expressions could act as a reference to evaluate metastasis and unfavorable prognosis of lung cancer.TIMP_1 was not simple response to local increase of MMP_9. S100A_4 was concerned with modulation of the expression of MMPs, which may inaugurate a new approach to lung cancer therapy.