Surgery-related change in cancer cell adhesion associates with recurrence in patients undergoing colorectal cancer surgery

Abstract

Objectives

This study aimed to investigate the effect of pre- and postoperative serum on the adhesion of cultured colon cancer cells and their relationship with colorectal cancer recurrence.

Background

Colorectal cancer is common, and surgery is the primary treatment choice. However, surgical procedures may be associated with an increased risk of recurrence.

Method

434 patients undergoing curatively intended colorectal cancer surgery at Copenhagen University Hospital, Herlev, Denmark, between July 15, 2014, and March 31, 2019, were included in the study. Pre- and postoperative serum samples were collected, and the effect on cellular adhesion was analyzed using a novel high-throughput approach based on CRISPR/Cas9 modified Caco-2 cells and secreted luciferase, named the AdhesionScore assay. The relative risk of postoperative recurrence was estimated using Cox proportional regression analysis.

Results

The difference in adhesion between modified Caco-2 cells seeded in the pre- and postoperative serum showed a significant increase in postoperative adhesion in patients with a recurrence event (p=0.0293). Modeling the adhesion data using multiple logistic regression and Cox proportional regression analyses showed a statistically significant association between increased postoperative adhesion and recurrence (p=0.0155 and p=0.0126, respectively). Patients with the highest AdhesionScore showed the greatest risk of recurrence (HR=7, 95% CI 1.6-37.8, p=0.0130).

Conclusions

The study found that a difference in the adhesion of Caco-2 cells seeded in pre- and postoperative serum was associated with cancer recurrence following intended curative surgery. This suggests that increased postoperative adhesion may serve as a novel biological marker of recurrence in patients undergoing surgery for colorectal cancer.