Abstract 3313: Plasma levels of MMP7 are significantly increased in patients with colorectal cancer compared to benign disease colon pathology

Abstract

Abstract Introduction: MMP-7 (matrilysin), a matrix metalloproteinase (MMP) family member, is expressed in epithelial cells and some cancers. MMP7 is capable of activating pro-collagenases and digesting extracellular matrix (ECM) proteins. MMP7 supports connective tissue remodeling and regulates intestinal host defense and innate immunity. Increased MMP7 expression is associated with inflammation, tumorgenesis, and metastasis. MMP7 regulates neutrophil recruitment at sites of neoangiogenesis. MMP7 is capable of activating pro-MMP-1,-2,and-9, and osteopontin. Preoperative (preop) colorectal cancer patient’s plasma levels of MMP2, MMP3 and osteopontin have been shown to be higher than benign disease patient’s preop levels. MMP7 overexpression is reported in many malignancies (colorectal cancer (CRC) included). This study’s purpose was to compare PreOp plasma MMP7 levels in CRC and benign colon disease (BCP) patients (pts). Method: Pts undergoing colorectal resection for CRC or BCP who were prospectively enrolled in an IRB approved tissue/data bank for whom plasma samples were available were studied. Clinical, demographic and pathological data were reviewed. Plasma MMP7 levels were determined via ELISA in duplicate and reported as median +95%CI (ng/ml). Expression levels were determined in tumors and paired normal colon tissues in a subgroup of study pts by QRT-PCR. The candidacy of MMP7 as a diagnostic marker for CRC was validated by the receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) results. The Mann-Whitney test was used for statistical analysis. Results: A total of 120 CRC (72% colon, 28% rectal) and 120 BCP pts (adenoma 33%, diverticulitis 52%, other 15%) were studied. The male: female ratios in both groups were similar but CRC pts were older. The CRC stage distribution was stage 1,30%; stage 2,27%, stage 3,33%, stage 4,10%. The median plasma MMP7 level was significantly higher in the CRC group than in the BCP group(3.69,CI: 3.39,4.07vs 2.79, CI: 2.51,3.2;P=< 0.001). The AUC for the ROC curve (AUC) for plasma MMP7 in association with a CRC diagnosis was 0.698 (sensitivity 48%, specificity 80%). All CRC tumors tested showed elevated MMP7 expression vs. paired normal tissue. Conclusion: The median PreOp plasma MMP7 level was 33% higher in CRC vs. BCP group. The AUC results suggest MMP7 may have value as a CRC prognostic marker, perhaps, in combination with other protein markers. High MMP7 levels may be related to tumor vascularization and inflammation associated with the cancer. Further studies that assess larger populations are needed to further assess preop MMP7 levels. Citation Format: HMC Shantha Kumara, Dasuni N. Gamage, Neil Mitra, Carl S. Winkler, Sandhu K. Jaspreet, Xiaohong Yan, Vesna Cekic, Hiromichi Miyagaki, Nipa D. Gandhi, Richard L. Whelan. Plasma levels of MMP7 are significantly increased in patients with colorectal cancer compared to benign disease colon pathology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3313.