Determining the Levels of Matrix Metalloproteinase-9 in Portal and Peripheral Blood is Useful for Predicting Liver Metastasis of Colorectal Cancer

Background: Matrix metalloproteinase-9 (MMP-9) is one of the MMPs that play an important role in cancer invasion and metastasis. Increased levels of MMP-9 in tumor tissue have been found to correlate with advanced stages of colorectal cancer. However, the clinical significance of determining the levels of MMP-9 in blood samples from patients with colorectal cancer has not yet been clarified. The purpose of this study was to clarify the relationship between the clinicopathological variables of colorectal cancer and MMP-9 levels of drainage (portal) or peripheral venous blood and to examine whether this assay would be useful for predicting liver metastasis. Methods: Blood samples were obtained from peripheral and drainage veins of 102 patients with colorectal cancer during surgery and the plasma levels of MMP-9 were determined by a one-step sandwich enzyme immunoassay. Results: The levels of portal MMP-9 were significantly higher than those of peripheral blood (P < 0.01, n = 102). The levels of MMP-9 in peripheral venous blood did not correlate with any of the 12 clinicopathological variables examined, while the levels of MMP-9 in portal blood correlated with macroscopic type of the primary tumor (P = 0.02), Dukes’ stage (P = 0.03), liver metastasis (P < 0.01) and lymph node metastasis (P = 0.02). By setting the cutoff ratio of portal to peripheral MMP-9 levels at 1.6 in patients with curative resection (n = 73), elevated ratios predicted subsequent emergence of liver metastases with 77.8% sensitivity, 81.3% specificity and 80.8% accuracy. Conclusion: The results suggest that synchronous determination of the levels of MMP-9 in portal and peripheral blood would be useful for selecting colorectal cancer patients at high risk of hepatic recurrence.