Colorectal cancer detection by biomarker quantification in noninvasively collected colorectal mucus: preliminary comparison of 24 protein biomarkers

Objectives Noninvasive colorectal cancer detection and screening remain global diagnostic challenges because the existing stool tests either lack sensitivity or are complex and expensive. Moreover, colorectal cancer screening uptake is low due to stool sampling inconvenience. We have developed a simple and patient-friendly noninvasive technique for collecting highly informative colorectal mucus. In this study, we aimed to comparatively assess a range of candidate biomarkers in colorectal mucus samples for colorectal cancer detection. Methods The study included 17 patients with colorectal cancer and 35 healthy controls, who provided noninvasively collected colorectal mucus samples. Protein biomarker quantification in these samples by enzyme-linked immunosorbent assays allowed comparing diagnostic performances of 24 candidate biomarkers that comprised haemoglobin, d-dimer, M2-pyruvate kinase, carcinoembryonic antigen, C-reactive protein, calprotectin, eosinophil-derived neurotoxin, protein S100A12, tumour necrosis factor alpha, clusterin, soluble cytokeratin 18, caspase-cleaved cytokeratin 18, citrullinated histone H3, peptidyl arginine deiminase 4, epidermal growth factor, epidermal growth factor receptor, matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 1, periostin, vascular endothelial growth factor A, vascular endothelial growth factor receptor 1, vascular cell adhesion molecule 1, intercellular adhesion molecule 1 and mucin 2. Tested biomarkers were ranked for colorectal cancer detection efficiency using receiver operating characteristic curve analysis. Results High area under the curve values between 0.943 and 0.768 were observed for haemoglobin, tissue inhibitor of metalloproteinase 1, M2-pyruvate kinase, peptidyl arginine deiminase 4, C-reactive protein, matrix metalloproteinase 9, epidermal growth factor receptor, eosinophil-derived neurotoxin and calprotectin. Conclusion Quantification of protein biomarkers in noninvasively collected samples of colorectal mucus certainly allows detecting colorectal cancer. Further clinical evaluation of the optimal biomarkers identified by this study is needed.