基质金属蛋白酶及组织抑制剂在肝癌中的表达及与预后的关系

目的：探讨基质金属蛋白酶（MMPs)及其组织抑制剂（TIMPs）在肝癌中的表达及其意义。方法：应用免疫组化、Northern印迹杂交及图像分析技术对人肝细胞癌（HCC）、肝癌细胞株7721、全反式维甲酸处理的7721细胞（RA－7721）和正常人肝细胞株L－02作MMP－1、2、9和TIMP－2的表达分析。结果;肝癌细胞浆内可表达MMP－1、2和9,但癌内阴性组5年生存率明显高于相应的阳性组（P＜0．05）。体外MMP－9mRNA在7721细胞表达明显高于RA－7721以及L－02细胞,而TIMP－2mRNA的表达与MMP－9相反,MMP－2mRNA在7721细胞中的表达仅略高于L－02细胞。结论：HCC组织内MMP－1和9的表达与患者的预后密切相关;癌细胞高表达MMP－9、低表达TIMP－2,可能是肝癌细胞浸润、转移的主要基础,而MMP-2并无重要作用。

Study of the expression of matrix metalloproteinase and its tissue inhibitor in hepatocellular carcinoma

Objective To study the expression of matrix metalloproteinase (MMP) and the tissue inhibitor of matrix metalloproteinase (TIMP) in hepatocellular carcinoma (HCC) and its relation with the prognosis of patient. Methods MMP 1,MMP 2,MMP 9 and TIMP 2 in human HCC tissue and HCC cell line were measured and quantified with immunohistochemistry, Northern blot hybridization and image analysis. Results MMP 1,MMP 2 and MMP 9 were localized in the cytoplasm of tumor cells. The 5 years survival rate were markedly higher in the cases of MMP 1 negative, MMP 9 negative, both MMP 1 and MMP 2 negative or both MMP 1 and MMP 9 negative staining than that of the positive cases ( P <0.05). In vitro the expression of MMP 9 mRNA in 7721 HCC cells was markedly higher than that in the normal hepatocyte cell line L 02 and 7721 HCC cells reversed with all trans retinoid acid (RA 7721), while the level of the expression of MMP 2 mRNA in 7721 HCC cells was only slightly higher than that of L 02 cells. In contrast to MMP 9, the expression of TIMP 2 mRNA in 7721 cells was significantly lower than that of L 02 cells. Conclusion The expressions of MMP 1 mRNA and MMP 9 mRNA was related to prognosis of patient. The increase of the expression of MMP 9 mRNA and the decrease of TIMP 2 mRNA might be the major basis of the tumor invasion and metastasis with a poor prognosis of HCC.