Abstract 3937: Minimally invasive colorectal resection (MICR) is associated with elevated plasma levels of Urokinase-type Plasminogen Activator-1 (uPA) from 2nd to 6th week after surgery which may promote tumor growth and metastasis
Authors: Mudiyanselage Chandana S K Herath , Shah Abhinit , Mitra Neil , Gamage Dasuni Niyagama , Yan Xiaohong , Cekic Vesna , Whelan Richard L. 
Published: September 2020

Introduction: Urokinase-type Plasminogen Activator-1 (uPA) is a secreted protease that activates Plasminogen to form Plasmin. uPA binds to the widely expressed uPA receptor (uPAR); uPA-uPAR complexes can be inhibited by Serpin E1/ Plasminogen activator inhibitor-1(PAI-1). Active plasmin catalyzes many physiopathological processes requiring basement membrane (BM) and/or extracellular matrix (ECM) remodeling. uPA together with uPAR and PAI-1 plays a wide role in regulating tumor cell proliferation, adhesion, migration, intravasation and metastasis. uPA and uPAR promote immune cell activation at sites of matrix remodeling during wound healing. uPA directly or via plasmin leads to activation of various angiogenic growth factors including VEGF and IGF. Over expression of uPA has been documented in several cancers including colorectal cancer (CRC) and high tissue levels correlated with a poor prognosis. The impact of minimally invasive colorectal resection (MICR) for CRC on plasma uPA levels is unknown. This study's aim was to measure plasma uPA levels during the first postoperative (postop) month.

Method: CRC patients (pts) undergoing MICR who were enrolled in an IRB approved data/plasma bank for whom adequate plasma was available were eligible. Clinical, demographic and pathological data were prospectively collected. Blood samples were collected PreOp and on postoperative day (POD) 1, 3 and at least 1 late timepoint (between POD7-41). Late samples were bundled into 7 day time blocks and considered as single time points. Total uPA levels were analyzed in duplicate via ELISA and the results reported as mean and ±SD. The Wilcoxon paired t-test was used for analysis (significance, p&lt;0.05).

Results: A total of 93 MICR CRC pts (colon 68%; rectal 32%; 46 male /47 female, mean age 65.6± 13.3 years) met the study criteria. The mean incision length was 7.0 ±4.1cm. The Cancer stage breakdown was; Stage I, 30%, Stage II, 30%, stage III, 33% and stage IV, 7%. The mean PreOp uPA level (ng /ml) was 598.6± 330.8 (n=93). Significantly elevated mean plasma levels were noted on POD3 (648.8±504.6, n=86, p= 0.003), POD7-13 (865.4±851.0, n=72, p&lt; 0.001), POD14-20 (1010±963.9, n=27, p&lt;0.001), POD 21-27 (672.8±232.8,n=15, p&lt;0.001) and on POD 28-41 (819.4±303.2, n=21, p&lt;0.001) when compared to PreOp levels.

Conclusion: Plasma uPA levels remained significantly elevated from preop levels from POD 3 through the 6th week after MICR for CRC. The increases were 11%-66% over baseline. Early increases may be related to the acute inflammatory response while the late elevations may be associated with wound healing related inflammation and angiogenesis. Increased uPA levels may promote metastases or the growth of residual cancer. Further study with larger population warranted.

Citation Format: Chandana S K Herath Mudiyanselage, Abhinit Shah, Neil Mitra, Dasuni Niyagama Gamage, Xiaohong Yan, Vesna Cekic, Richard L. Whelan. Minimally invasive colorectal resection (MICR) is associated with elevated plasma levels of Urokinase-type Plasminogen Activator-1 (uPA) from 2nd to 6th week after surgery which may promote tumor growth and metastasis [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 3937.