Abstract 1145: Assessing the diagnostic value of the combination of Matrix Metalloproteinase 2 (MMP2) and Progranulin (PGRN) preoperative plasma levels for colorectal cancer (CRC)

Abstract

Abstract Introduction: MMP 2, also known as Gelatinase A, is an extracellular matrix remodeling enzymes. MMP-2 activity is regulated by various oncogenes, cytokines and growth factors. MMP 2 functions in the breakdown of extracellular matrix (ECM) and participates in tumor neoangiogensis. It is also associated with an angiogenic and metastatic tumor cell phenotype, in vivo. Up-regulation of MMP-2 aggravates the loss of basement membrane type IV collagen, breaks down ECM and promotes tumor progression and invasion. Progranulin (PGRN) is a ubiquitously expressed secreted glycoprotein that activates both the PI3k and ERK pathways, and promotes cyclin D1 and cyclin B expression which supports proliferation and survival of mesenchymal and epithelial origin cells. PGRN stimulates VEGF expression in breast cancer cells, in vitro, and stimulates inflammation, fibroblast accumulation and angiogenesis. Over-expression of MMP2 and PGRN has been reported in many cancers including CRC. The aim of this study was to compare preoperative (preop) plasma MMP2 and PGRN levels in CRC and benign colonic disease (BCD) patients (pts), alone and in combination, as a means of detecting CRC. Method: Preop plasma samples were obtained from consenting CRC and BCD pts undergoing elective resection for whom adequate preop plasma was available from an IRB approved tissue bank. Demographic, clinical, and pathologic data were collected. PreOp plasma levels of MMP2 and PGRN (ng/ml) were determined via ELISA in duplicate and reported as median + 95%CI. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to assess single or multiple plasma protein levels as a diagnostic tool for CRC. The Mann-Whitney test was used for statistical analysis (significance p<0.05). Results: A total of 172 CRC pts (70% colon, 30% rectal) and 102 BCD pts (adenoma 33%, diverticulitis 54%, other 15%) were eligible for the study. The CRC pathologic stage distributions were: Stage-I, 25%; Stage-2, 32%, Stage-3, 31%, Stage- 4, 12%. Median preop plasma protein levels in CRC pts were significantly higher than BCD pts. [MMP2; 205.3,CI 198.2,217.5 vs.165.3,CI 156.8,179.1: PGRN; 54.7,CI 51.8,57.1 vs.43.3,CI 40.1,46.8,P<0.001) The AUC value for ROC curve for MMP2 and PGRN were 0.721 and 0.724 respectively with 73% and 71% specificity. AUC for the combination of these 2 proteins was 0.757 with 97% specificity. Conclusion: Median MMP2 and PGRN levels were higher in CRC pts and the CRC median values were 24% and 26% higher than BCD median levels respectively. ROC curve analysis showed that the two protein combination improved specificity and AUC values. MMP2 and PGRN are potential candidates for a larger diagnostic panel to include other proteins found to be elevated in CRC pts. Further study is warranted. Citation Format: Chandana S K Herath Mudiyanselage, Neil Mitra, Dasuni Niyagama Gamage, Hiromichi Miyagaki, Abhinit Shah, Xiaohong Yan, Vesna Cekic, Richard L. Whelan. Assessing the diagnostic value of the combination of Matrix Metalloproteinase 2 (MMP2) and Progranulin (PGRN) preoperative plasma levels for colorectal cancer (CRC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1145.