Abstract 3853: Plasma activin A levels are significantly elevated for a month after minimally invasive colorectal resection (MICR) for cancer and may support early growth of residual tumor

Abstract Introduction: Activin A (ActA) is a cytokine from the TGF-β family. ActA has a wide range of effects in different tissues and plays a role in inflammation, fibrosis, and wound healing. Its actions are mediated mainly via SMAD signaling. A variety of tumors express ActA which has been associated with increased MMP levels and tumor invasion. ActA is also found in the tumor microenvironment (fibroblasts, EC’s, and immune cells). ActA mediates the development of cancer-associated fibroblasts that facilitate tumor invasion. Higher tumor ActA levels are associated with worse outcomes. Surgery’s impact on ActA levels is not understood. This study’s purpose was to determine plasma ActA levels before and after MICR for colorectal cancer (CRC). Method: CRC patients (pts.) undergoing MICR enrolled in an IRB approved data/tissue bank for whom periop plasma samples were available were eligible. Clinical and pathological data was collected prospectively. Blood samples were obtained preoperatively (PreOp) and on various postoperative days (POD) including POD 1, 3, and at least one late postoperative day (POD 7 to 41). Late samples were grouped into 7-day bundles and used as single time points. Plasma ActA levels were measured in duplicate via ELISA and results expressed as mean ±SD. The Wilcoxon paired t-test was used (sig. p<0.05). Correlation between plasma ActA levels and incision length, surgical length, etc was determined using Spearman's rank correlation (rs.). Plasma Act A levels between Laparoscopic and hand-assisted groups were compared by Mann-Whitney U test. Results: A total of 83 CRC MICR patients met inclusion criteria (48 males: 35 females mean age 65.31± 14.09; rectal, 32%/colon, 68%). The mean incision length was 8.21± 3.63 cm and mean length of stay was 7.9± 6.9 days. The cancer staging (STG.) breakdown was; STG I, 40%, STG II, 29%, STG III, 28% and STG IV, 3%. The mean PreOp ActA level (pg/ml) was 235.8±119.8 (n=83). Elevated mean plasma levels were noted on POD 1(300.4±150.1, n=82, p< 0.001), POD3 (325.0±217.4, n=72, p< 0.001), POD7-13 (314.9±245.4, n=57, p=0.03), POD14-20 (316.0±144.8, n=29, p=0.003), POD 21-27 (279.3±115.7, n=15, p=0.03) and on POD 28-41(246.4±86.86, n=18, p=0.02) when compared to PreOp levels. Postop ActA levels correlated with the duration of surgery on POD1 (rs = 0.3, p= 0.002). The mean ActA levels in the hand group were elevated at all Postop time points (9-26%) with (sig. only POD1;P=0.02). Conclusion: Plasma ActA levels remained significantly elevated from preop levels for 6 weeks after CRC MICR. The increases were 37-39% over Preop levels. The source of the increase may be linked to inflammation associated with wound healing and angiogenesis. Elevated plasma ActA concentrations could potentially facilitate metastasis or the proliferation of remaining cancer cells during the initial month post-surgery. Citation Format: Chandana S. K. Herath Mudiyanselage, Yi-Ru Chen, Neil Mitra, Hiromichi Miyagaki, Elizabeth Nilsson Sjolander, Xiaohong Yan, Vesna Cekic, Richard L. Whelan. Plasma activin A levels are significantly elevated for a month after minimally invasive colorectal resection (MICR) for cancer and may support early growth of residual tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3853.