Abstract 763: Minimally invasive colorectal resection is associated with significantly elevated plasma levels of extracellular cold inducible RNA binding protein for a month after colorectal resection & may promote the growth of residual metastases
Authors: Mudiyanselage Chandana S. K. Herath , Yan Xiaohong , Mitra Neil , Angammana Hansani N. , Morrar Doaa F. , Chia Vincent , Hedjar Yanni , Cekic Vesna , Agnew Jennifer L. , Whelan Richard L. 
Published: April 2023

Introduction: Cold-Inducible RNA-Binding Protein (CIRP) is similar to a class of stress-induced RNA binding proteins and is mostly found in the nucleus where it regulates transcription. In response to stress, CIRP moves to the cytoplasm where it regulates translation; a fraction of the cytoplasmic CIRP is released extracellularly (eCIRP). eCIRP is a damage-associated molecular pattern (DAMP) molecule that promotes inflammatory responses including TNF-alpha, IL-6, and HMGB production. Lymphocytes, macrophages, and PMN’s are activated after surgery and can generate eCIRP. Elevated eCIRP blood levels may impact macrophage function and induce immune tolerance that may promote tumor growth and progression. This study’s purpose was to measure plasma eCIRP levels before and for a month after MICR for CRC.

Methods: CRC patients (pts) in an IRB approved data/tissue bank who underwent MICR for whom plasma was available were selected. Demographic, clinical and pathology data were reviewed. Plasma samples were collected preoperatively (preOp) and at 6 post-operative (Postop) time points (POD 1, 3, 7-13, 14-20, 21-27, 28-41); samples were processed and frozen until used. Late samples were bundled into 7-day blocks and considered as single time points. eCIRP levels were analyzed in duplicate using ELISA. The Wilcoxon paired t-test was used for analysis.

Results: 83 CRC pts who underwent MICR were studied (colon 66%, rectal 34%; mean age 65); 26% had Hand assisted (HA) MIS (mean incision length[IL] 10.0±2.9cm) and 69% laparoscopic (LAP, mean IL 6.9±4.1cm) MICR. The cancer stage breakdown was; I, 30%; II, 32%; III, 35% and IV, 3%. The mean PreOp eCIRP level was 896.8± 757.0pg/ml; vs. preop levels increased mean plasma levels (p=&lt;0.001) were noted on POD1 (2549± 2632pg/ml, n= 83), POD3 (1871± 1362pg/ml, n= 77), POD7-13 (1788± 1403pg/ml, n=57), POD14-20 (1473± 738.8pg/ml, n=30), and POD 21-27 (1681± 1375pg/ml, n= 21). With regard to MIS method, greater eCIRP increases were noted in the HA vs the Lap group from POD1-POD20 (p=0.01-0.04).

Conclusions: Plasma eCIRP levels are elevated for a month after MICR for CRC (% change range 100-184) and peaked on POD1. The cause of the early increase may be the acute inflammatory response whereas the late elevations may be related to wound healing-related tissue remodeling. Higher mean levels in the HA vs Lap group suggests that the extent of surgical trauma impacts eCIRP levels postop. Previous studies noted increased post-MICR plasma levels of MCP-1, CHI3L1 and IL8 that stimulate macrophage activity. eCIRP, together with those proteins may promote macrophage recruitment and function and might promote the growth of residual tumor deposits postop. Further studies are warranted.

Citation Format: Chandana S. K. Herath Mudiyanselage, Xiaohong Yan, Neil Mitra, Hansani N. Angammana, Doaa F. Morrar, Vincent Chia, Yanni Hedjar, Vesna Cekic, Jennifer L. Agnew, Richard L. Whelan. Minimally invasive colorectal resection is associated with significantly elevated plasma levels of extracellular cold inducible RNA binding protein for a month after colorectal resection & may promote the growth of residual metastases [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 763.