Association of Circulating Protein Biomarkers of Gut Barrier Integrity and Inflammation with Colorectal Adenomas and...

Loss of gut barrier integrity, bacterial translocation and related inflammation are emerging etiological links in the development and progression of colorectal cancer (CRC).

This study investigated associations between circulating biomarkers of gut barrier functionality and inflammation with colorectal adenoma (CRA, n = 49), CRC (n = 108), and controls (n = 101) in case-control studies from Ireland and the Czech Republic.

Circulating concentrations of the biomarkers were measured using enzyme-linked immunosorbent assay (ELISA), and Mesoscale Discovery immunoassays. Multivariable logistic regression was used to generate odds ratios (ORs) and 95% confidence intervals (CIs), analysing the associations between the biomarkers and disease stages. Diagnostic performance was assessed through receiver operating characteristic (ROC) curves and area under the curve (AUC) analysis.

Higher calprotectin concentrations were positively associated with CRC in both Irish and Czech cohorts and in the combined meta-analysis (OR = 1.81, 95% CI: 1.10-2.96; OR = 1.98, 95% CI: 1.27-3.11; OR = 1.16, 95% CI: 1.00-1.35, respectively). IL-8 was positively associated with CRC in the Czech cohort and the meta-analysis (OR = 2.43, 95% CI: 1.32-4.48 and OR = 1.92, 95% CI: 1.29-2.86, respectively). The optimal diagnostic biomarker combination in the meta-analysis included calprotectin, IL-8, lipopolysaccharide binding protein (LBP), and C-reactive protein (CRP), achieving an AUC of 0.70 (95% CI: 0.61-0.79).

Our results suggest that a dysfunctional gut barrier may contribute to development and progression of colorectal neoplasia, while combinations of proteins involved in gut integrity may serve as diagnostic biomarkers.