Clinicopathologic and Prognostic Significance of Gelatinase A in Tunisian Colorectal Cancer: A Case-Control Study.

ABSTRACT

Matrix metalloproteinase-2 (gelatinase A) is a well-known mediator of cancer metastasis, but it is also thought to be involved in several aspects of cancer development, including cell growth and inflammation. In the present study, we investigate whether MMP-2 SNP, MMP-2 mRNAs, and MMP-2 protein are associated with the susceptibility to colorectal cancer in the Tunisian population. The TaqMan allele discrimination assay and DNA sequencing techniques were used for genotyping; MMP-2 expression of each genotype was analyzed by semiquantitative RT-PCR, and MMP-2 protein expression was analyzed by immunohistochemistry staining. Our result showed that the levels of MMP-2 mRNA expression in patients containing the CC genotype were much higher compared with cells with the CT genotype. The frequency of the MMP-2 CC genotype was significantly higher in colorectal cancer patients when compared with controls (OR=1.94; 95% CI, 1.117-3.680). A higher intensity of staining of MMP-2 was observed in regions of invasion of the muscularis mucosa compared with superficial portions of the tumor. In addition, we found a significant progressive increase in total MMP-2 plasma levels with progression from adenomatous polyps through advancing Dukes stages (P=0.0001). Our data suggest that MMP-2 may be associated with colorectal cancer development and invasion in the Tunisian population; moreover, SNP and levels of MMP-2 could be a predictive value for colorectal cancer prevention and invasiveness.