Serum Matrix-Metalloproteinase-1 is a Bona Fide Prognostic Marker for Colorectal Cancer

Abstract

Matrix metalloproteinases (MMPs) are involved in the degradation of extracellular matrix components and are associated with invasion and metastasis. MMP proteins could be serum tumor markers or molecular targets in the treatment of malignancy. The purpose of the current study was to identify a prognostic serum marker in cases of colorectal cancer (CRC) prior to surgical intervention. Laser microdissection and microarray analysis were used to characterize gene expression in 73 cases of CRC. We then focused on expression of MMP-1. We examined serum MMP-1 activity before resection in another subset of 75 cases of CRC to validate the clinical significance of MMP-1 as a prognostic marker in CRC after surgically curative operation. Disease-free survival was 51% in the MMP-1 high expression group and 81% in the low-expression group (P < .05). Survival was 52% in the MMP-1 high expression group and 90% in the low group (P < .05). In multivariate analysis for disease-free survival, MMP-1 and lymph node metastasis were significant independent prognostic indicators. In multivariate analysis of overall survival, serum MMP-1 level was the only significant independent indicator among factors. Within the MMP family of proteins, MMP-1 is not a cancer-specific protease. However, MMP-1 activity does predict the future course of progression of malignant cells. Thus, MMP-1, which is activated at the primary lesion and is found in serum, assists in the clinical diagnosis of CRC. It is also an important molecule for understanding the underlying mechanism of invasion and metastasis of CRC.