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
Authors: Herath Mudiyanselage Chandana S. k. , Miyagaki Hiromichi , Mitra Neil , Hedjar Yanni , Yan Xiaohong , Cekic Vesna , Martz Joseph , Agnew Jennifer , Whelan Richard L. 
Published: June 2022

Abstract
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&lt;0.0001). Higher OPN levels were noted in stg 3(p=0.04) and Stg 4(p=0.01) vs stg 1 pts. The AUC value for the ROC curve for OPN and MMP2 were 0.73 and 0.73 respectively with 61% and 70% specificity. The AUC for the 2 protein combination was 0.80 with 65% sensitivity and 80% specificity. OPN and MMP2 expression was elevated in 75% and 50% of CRC tumors tested, respectively (n=12).
Conclusion: Median CRC OPN and MMP2 levels were significantly higher (39% and 27%) than BP levels. OPN and MMP2 expression was confirmed in a subset of pts. This 2 protein combination improved the AUC and specificity for CRC diagnosis. Further study with more protein combinations is warranted.
Citation Format: Chandana S. k. Herath Mudiyanselage, Hiromichi Miyagaki, Neil Mitra, Yanni Hedjar, Xiaohong Yan, Vesna Cekic, Joseph Martz, Jennifer Agnew, Richard L. Whelan. 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 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1415.