Abstract 5392: Plasma levels of Matrix metalloproteinases 9, an angiogenic promoting protein, are persistently elevated three weeks after minimally invasive colorectal resection (MICR) for cancer which may support residual tumor metastasis
Authors: Mudiyanselage Chandana S. K. Herath , Sharma Anuj R. , Mitra Neil , Sah Aashutosh , Yan Xiaohong , Palacios Pablo , Cekic Vesna , Whelan Richard L. 
Published: March 2024

Introduction: The Matrix metalloproteinases (MMPs) family are a collection of zinc and calcium-dependent endopeptidases. MMP-9 is instrumental in modifying the extracellular matrix (ECM) and generating bioactive molecules which influence a range of physiological functions. Cellular TNF-a, IL-8, VEGF, and FGF-2 can stimulate the production of MMP-9 in endothelial cells (EC), a process that controls healthy and disease-related angiogenesis. MMP-9 facilitates tumor metastasis and also is involved with wound healing. MMP-9 is generated by white blood cells, ECs, and several other cells. There’s a significant increase in plasma MMP-9 levels in patients suffering from colorectal cancer (CRC). The aim of this study was to assess plasma MMP-9 levels before and during the first month following MICR for CRC.

Method: CRC patients enrolled in an IRB approved data/plasma bank who had undergone MICR for whom plasma samples were available from the following time points were deemed eligible for this study; preoperatively (PreOp) and on Postoperative Day (POD) 1, POD 3 and at least 1 later postop timepoint (POD 7-41). The demographic, clinical operative and pathology reports were reviewed. Blood specimens were collected, processed, and frozen. MMP-9 levels were measured in duplicate via ELISA. The Wilcoxon paired t-test was used for analysis and significance set at p&lt;0.05.

Results: 86 CRC MICR patients (69% colon,31% rectal; laparoscopic 69%, hand-assisted 31%; 47 males, 39 females; mean age 63.9± 14.3 years), met the entry criteria. The mean hospital stay was 6.5±3.0 days. The cancer stages were distributed as follows: stage I; (n=26), II; (n=25), III; (n=30), and IV; (n=4). Compared to the mean preop MMP-9 plasma levels (155.3±132.1,n=86; ng/ml), there was a significant increase on postoperative day (POD) 1 (292.6± 213.0; n=86, p&lt;0.001), POD3 (232.1±205.9,n=78, p&lt;0.01), POD7-13 (217.8±171.2, n=63, p&lt;0.01), POD14-20 (228.7± 109.1,n=24,p=03). No difference was found at the POD 21-41 time points vs preop results. Non-significant increases in plasma MMP-9 levels were noted in the hand-assisted surgery group during the POD 3-27 period compared to the laparoscopic group.

Conclusion: Postop plasma MMP-9 levels were significantly elevated (20% - 88%) vs preop levels for 3 weeks after MICR for CRC. The increased MMP-9 levels in the early postoperative period may be due to the acute inflammatory response, including increases in IL-1 and TNF mediated activation of neutrophils and macrophages. However, the spike during weeks 2-3 may be related to wound healing given MMP-9’s role in angiogenesis. This persistent elevation for 3 weeks after surgery may also enhance angiogenesis in residual cancer deposits postoperatively. Further studies are needed.

Citation Format: Chandana S. K. Herath Mudiyanselage, Anuj R. Sharma, Neil Mitra, Aashutosh Sah, Xiaohong Yan, Pablo Palacios, Vesna Cekic, Richard L. Whelan. Plasma levels of Matrix metalloproteinases 9, an angiogenic promoting protein, are persistently elevated three weeks after minimally invasive colorectal resection (MICR) for cancer which may support residual tumor metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5392.