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Back to 2014 Annual Meeting Posters Plasma Levels of Matrix Metalloproteinase 3 (MMP3) Is Significantly Increased in Patients With Colorectal Cancer H M C. Shantha Kumara*1, Xiaohong Yan1, Hiromichi Miyagaki1,2, Jeanine Arkenbosch1, Sahani De Silva1, Linda Njoh1, Vesna Cekic1, Richard L. Whelan1 1Division of Colon and Rectal Surgery, Department of Surgery, St Lukes Roosevelt Hospital Center, New York, NY; 2Department of Gastroenterological surgery,, Osaka University 2-2, Yamadaoka, Suita,, Osaka,, Japan Introduction: MMP3, a member of the matrix metalloproteinase (MMPs) family, plays a role in the breakdown of extracellular matrix (ECM) and connective tissue remodeling and is thought to facilitate solid tumor progression and metastasis. MMP3 biosynthesis is regulated by epidermal growth factor, TNF- α, and IL1; the active form of MMP3 stimulates the epithelial-mesenchymal transition (EMT) during tumor development. Together with its activator, matriptase, MMP3 may promote tumor angiogenesis and growth via regulation of VEGF bioavailability. MMP3 over expression has been demonstrated in many malignancies including breast, lung, and ovarian cancer. Plasma MM3 levels in colorectal cancer (CRC) patients (pts) have not been well studied. This study's purpose was to compare plasma MM3 levels in pts with CRC and benign colonic pathology (BCP). Method: Preoperative (PreOp) plasma samples were obtained from CRC and BCP pts undergoing elective resection. Clinical, demographic and final pathological data were prospectively collected. Plasma MMP3 levels were determined via ELISA in duplicate and are reported as median + 95%CI (ng/ml). Expression levels were determined in the tumors and paired normal tissues of a subpopulation of study patients by QRT-PCR. The candidacy of MMP3 as a diagnostic marker for CRC was validated by the receiver operating characteristic (ROC) curve and by the area under the ROC curve (AUC) results. The Mann-Whitney test was used for statistical analysis, (significance p<0.05). Results: The study population consisted of 182 CRC (62% colon, 28% rectal) and 82 BCP pts (adenoma 26%, diverticulitis 67%, other 7%). CRC pts were older (mean age 67 vs.58, p<0.001) but the male/female ratios were similar. The median PreOp plasma MMP3 level was higher in the cancer pts (14.6, CI: 13.7, 15.8) than the BCP group (9.3, CI: 8.5, 10.5, p<0.001).The CRC stage distribution was: Stage-1, 24%; Stage-2, 37%, Stage-3, 29%, Stage- 4, 10%. Plasma MMP3 levels were significantly higher in the Stage 3 and 4 pts than in the stage 1 group ( p=0.01).The AUC value for the ROC curve (which assesses the diagnostic potential of plasma MMP3 levels) was 0.759(sensitivity 75%, specificity 67%). MMP3exprersion was elevated in all CRC tumors tested vs. paired normal tissues (n=28). Conclusion: The median plasma MMP3 level in the setting of CRC was 55% higher than noted in the BCP group (p<0.001). Plasma MMP3 levels were higher in stage 3 and 4 versus the stage 1 pts.AUC levels suggest MMP3 may have value as a prognostic marker for CRC. The source of the additional MMP3 is likely the tumor and stroma. In addition, inflammatory cells in the peritumor environment, via cytokine elaboration, may enhance MMP3 expression in tumor and stromal cells and, thus, contribute to the higher plasma MMP3 levels. Further study with larger populations of control and CRC pts is warranted. Back to 2014 Annual Meeting Posters |
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