Discovery of novel plasma proteins as biomarkers for the development of incisional hernias after midline incision in colorectal cancer patients: the ColoCare Study

Abstract

Background

Ventral incisional hernia is the most common long-term complication after abdominal surgery. Among newly-diagnosed colorectal cancer patients, we screened the pre-surgical plasma proteome to explore predictive markers for the development of an incisional hernia.

Methods

We utilized pre-operative plasma samples of 72 newly diagnosed colorectal cancer patients who underwent midline incision for tumor resection between 2010 and 2013. 21 patients with incisional hernia occurrence were matched with 51 patients with at least 18 months follow-up without an incisional hernia by gender, age, and BMI. To assess predictive markers of incisional hernia risk we screened the plasma proteome for >2,000 distinct proteins using a well-validated antibody microarray test. Paired t-tests were used to compare protein levels between cases and controls. A gene-set-enrichment analysis (Gene Ontology and KEGG) was applied to test for differences in signaling pathways between the two groups.

Results

The proteome screen identified 25 proteins that showed elevated or reduced plasma levels in the hernia group compared to the control group (nominal p-values <0.05). Several proteins were in pathways associated with wound healing (CCL21, SHBG, BRF2) or cell adhesion (PCDH15, CDH3, EPCAM).

Conclusion

Our study shows that there are multiple individual and groups of plasma proteins that could feasibly predict the personal hernia risk prior to undergoing surgery. Further investigations in larger independent sample sets are warranted to replicate findings and validate clinical utility of potential biomarkers. After validation, such a biomarker could be incorporated into a multifactorial risk model to guide clinical decision making.