Profile of Expression of Genes Encoding Matrix Metallopeptidase 9 (MMP9), Matrix Metallopeptidase 28 (MMP28) and TIMP Metallopeptidase Inhibitor 1 (TIMP1) in Colorectal Cancer: Assessment of the Role in Diagnosis and Prognostication
Zbigniew Lorenc, Dariusz Waniczek, Katarzyna Lorenc-Podgórska, Wiktor Krawczyk, Maciej Domagała, Mateusz Majewski, Urszula Mazurek
Chair and Clinical Department of General, Colorectal and Trauma Surgery, Medical University of Silesia, Sosnowiec, Poland
Med Sci Monit 2017; 23:1305-1311
Studies on the pathomechanism of colorectal cancer (CRC) expansion indicate a significant role of metalloproteinases and their inhibitors in the extracellular matrix. The results of the analysis of a profile of transcriptional activity of genes encoding metalloproteinases were the basis of the hypothesis indicating changes in the expression of genes encoding MMP9, MMP28, and TIMP1 as an additional diagnostic and prognostic marker of CRC.
MATERIAL AND METHODS: The material consisted of samples obtained from resected tumors and healthy tissue samples from 15 CRC patients (aged 46–72 years) at clinical stages (CSs) I and II–IV.
Gene expression analysis was done using microarrays. Microarray data analysis was done using the GeneSpring 11.5 platform. The results were validated using the qRT-PCR technique.
RESULTS: We found high levels of expression of MMP9 at each CS, as well as in the tissues at the early stage of CRC. Additionally, we observed high levels of expression of TIMP1 and low levels of MMP28 genes in CS II–IV. No statistically significant differences based on the stage of CRC were observed.
CONCLUSIONS: MMP9 gene profile may be a complementary diagnostic marker in CRC. The results suggest a crucial role of MMP9 at the early stage of carcinogenesis in the large intestine. The increase in MMP9 and TIMP1 mRNA concentration and the decrease in MMP28 in the large intestinal tissue may be a confirmation of cancer, but it may not indicate the advance of CRC.
Keywords: Colorectal Neoplasms, Gene Expression Profiling, Matrix Metalloproteinase 9, Matrix Metalloproteinase Inhibitors, Matrix Metalloproteinases