Abstract 3295: Plasma and tumor expression levels of progranulin osteopontin & matrix metalloproteinase 2 in colorectal cancer patients and assessment of plasma levels for diagnosis
Authors: Mudiyanselage Chandana S. K. Herath , Yan Xiaohong , Mitra Neil , Angammana Hansani N. , Miyagaki Hiromichi , Yanni Yanni , Cekic Vesna , Martz Joseph , Whelan Richard L. 
Published: April 2023

Introduction: PGRN is a growth factor involved in the regulation of cell proliferation, differentiation and pathological processes. OPN is an integrin binding phosphorylated glycoprotein involved in cell-mediated immunity, inflammation, cell survival, and tumor progression. MMP 2 is an extracellular matrix (ECM) remodeling enzyme that breaks down the ECM and also facilitates cancer growth. OPN promotes ERK pathway and VEGF mediated tumor angiogenesis and progression. PGRN stimulates VEGF expression in breast cancer cells in vitro. This study’s goals were to assess: 1) preoperative (preOp) plasma PGRN, OPN and MMP 2 levels in CRC and benign pathology (BP) patients (pts.), 2) tumor mRNA expression, and 3) the diagnostic potential of these proteins.

Method: CRC and BP bowel resection pts enrolled in an IRB approved tissue bank for whom preOp plasma was available were studied. Basic demographic, clinical, operative, and pathology data were evaluated. Plasma PGRN, OPN and MMP2 levels (ng/ml) were measured in duplicate via ELISA (results: median + 95%CI). Also, protein expression levels in tumors and paired normal tissue were determined for a subset of pts by QRT-PCR. CRC and BP plasma levels were compared by the Mann-Whitney test (significant &lt;0.05). The plasma receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate single and combined proteins levels.

Result: Plasma from 102 BP (adenoma 32%, diverticulitis 53%, other 15%) and 172 CRC (70% colon, 30% rectal) pts. were analyzed. The CRC Stage (STG) distribution was: STG-1, 25%; STG-2, 32%, STG-3, 31%, STG- 4, 12%. Median PreOp proteins levels in CRC patients for all 3 proteins were significantly higher than BP levels (PGRN; 54.71, CI: 51.82,57.12 vs. 43.32, CI: 40.10,46.89; OPN; 82.38, CI: 77.1,89.38 vs. 63.86, CI: 54.95,69.03; MMP2; 205.3 CI:198.2,217.15 vs. 165.3 CI: 156.83,179.06; P&lt;0.0001 for all). Plasma OPN levels were significantly higher in STG 4 pts vs STG 1 group ( p&lt;0.01). The percentage of tumors overexpressing these proteins were: PGRN, 8%; OPN, 77%; and MMP2, 59%. The single AUC values from the ROC curve for PGRN, OPN and MMP2 were 0.724, 0.703 and 0.721 with 71%, 77% and 73% specificity and with 63%, 55% and 64% sensitivity. The 3 protein combination achieved a specificity of 78% (AUC, 0.792) and sensitivity of 71%.

Conclusion: Median PGRN, OPN and MMP2 plasma levels in CRC pts were significantly higher (26%, 29% & 24% respectively) than BP levels; the OPN and MMP2 increases may be related to tumor expression. Increased plasma PGRN and MMP2 may be the result of tumor angiogenesis and inflammation-induced tissue remodeling. OPN levels were increased in stage 4 pts. The 3 protein combination had improved AUC & specificity vs single protein results. Further study is needed.

Citation Format: Chandana S. K. Herath Mudiyanselage, Xiaohong Yan, Neil Mitra, Hansani N. Angammana, Hiromichi Miyagaki, Yanni Yanni, Vesna Cekic, Joseph Martz, Richard L. Whelan. Plasma and tumor expression levels of progranulin osteopontin & matrix metalloproteinase 2 in colorectal cancer patients and assessment of plasma levels for diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3295.