Abstract 1415: Osteopontin and matrix metalloproteinase 2 plasma levels are elevated in colorectal cancer (CRC) vs benign disease; The 2 protein combination improves specificity as regards CRC diagnosis

Introduction: Expression of Osteopontin (OPN) and Matrix Metalloproteinase 2 (MMP 2) are elevated in CRC. OPN is an integrin binding phosphorylated glycoprotein implicated in cell-mediated immunity, inflammation, tumor progression, and cell viability. OPN is secreted by macrophages and leukocytes. OPN activity is associated with the PI3K/AKT and ERK pathways and VEGF mediated tumor angiogenesis. MMP-2 degrades type IV collagen and facilitates tumor cell invasion and metastasis. MMP-2 also promotes tumor angiogenesis. This study’s first purpose was to compare preoperative (PreOp) plasma OPN and MMP2 levels in CRC and benign pathology (BP) patients (pts); the 2nd purpose was to assess the combination of these proteins for diagnosis. Method: PreOp plasma samples obtained from consenting CRC and BP pts undergoing surgery were used for this study. Prospectively gathered demographic, clinical and pathologic data were analyzed. Plasma levels of OPN and MMP2 (ng/ml) were measured via ELISA and reported as median + 95% CI. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the diagnostic value of each protein alone and in combination. Expression levels of OPN and MMP2 were determined in tumor and normal tissue for a subset of pts by QRT-PCR. The Mann-Whitney test was used for analysis. Results: Plasma from 156 CRC (73% colon, 27% rectal) and 102 BP (polyp 32%, diverticulitis 56%, other 12%) pts was studied. CRC stage breakdown was: 1, 26%; 2, 33%, 3, 29%, 4, 12%. CRC median preop plasma levels were significantly higher vs. the BP group for both proteins [OPN; 82.4,CI:75.4, 89.5 vs 59.2, CI:53.8,63.3;MMP2; 203.6,CI:195.0,214.5 vs 160.2,CI:151.9,172.2; P