Relationship between matrix metalloproteinase 2 and lung cancer progression.

摘要

BACKGROUND AND OBJECTIVE: Matrix metalloproteinases (MMPs) play an important role in several steps of cancer development. MMP2 and MMP9 have previously been implicated in lymphatic and vascular invasion of lung cancer; however, the expression and prognostic significance of MMP2 and MMP9 is not fully clarified. This study was designed to investigate the significance of MMP2 and MMP9 in lung cancer tissue or serum, and their correlation with lung cancer prognosis. METHODS: Immunohistochemical analysis was performed to determine MMP2 and MMP9 staining in human nonsmall cell lung cancer (NSCLC). Serum MMP2 and MMP9 protein levels in patients after surgery were measured using the ELISA method. The correlation between MMP2 and MMP9 serum levels and clinicopathological features of NSCLC were analyzed by survival analysis. We also performed reverse transcriptase (RT)-PCR assays to detect messenger RNA (mRNA) expression to further confirm the activity of MMP2 and MMP9 in human lung cancer. RESULTS: Increased MMP2 immunostaining and MMP2 serum level correlated with advanced tumor stage and the presence of distant metastasis (Pearson's chi(2) test and ANOVA, p < 0.05). However, for MMP9, only serum level showed a correlation with advanced tumor stage. No significant correlation was observed between MMP2 or MMP9 immunostaining expression and tumor histologic features (Pearson's chi(2) test, p = 0.061 and p = 0.087, respectively). A high densitometry value of MMP2 and MMP9 PCR products (i.e. mRNA expression level) was related to poor differentiation grade, distant metastasis, and small cell carcinoma histologic type (ANOVA, p < 0.05). CONCLUSIONS: Our results suggest that MMP2 is a more sensitive predictor than MMP9 of lung cancer progression, metastasis, and survival. Serum MMP2 levels may be a valuable prognosis variable and could help to stratify lung cancer patients into low- and high-risk groups.