Abstract
Abstract Objectives An anal fistula is an external abnormal anatomical connection between the rectum and the outer skin of the anus. Symptoms include anorectal pain, abscesses, perianal cellulitis, smelly or bloody drainage of pus, and, in some cases, difficulty controlling bowel movements. Diagnosis and evaluation of anal fistulas is crucial for prognosis and for the choice of the treatment method. In this study, we aimed to discover potential biomarkers from serum proteins for the prediction of anal fistulas. Methods Using antibody array technology, the expression of 40 proteins was simultaneously detected in serum samples from 13 patients with anal fistulas with chronic diarrhea, 14 patients with chronic diarrhea and six healthy volunteers. Differentially expressed proteins were subsequently validated by ELISA, with a sample population expanded to 30 patients with anal fistulas and chronic diarrhea, 30 patients with chronic diarrheas only and 20 healthy controls. Results Quantification analysis identified MIP-1α, MIP-1β and TNF-R1 with significant differential expression between the anal fistula with chronic diarrhea, chronic diarrhea only and healthy control groups. Bioinformatics analyses, including PCA and heat map creation, showed a clear separation between the three groups using the expression of MIP-1α, MIP-1β and TNF-R1. Validation by ELISA with the expanded sample population fistulas showed significant differential expression levels of MIP-1α, MIP-1β and TNF-R1, displaying accuracy rates of 0.898, 0.987 and 1.0 between the anal fistula with chronic diarrhea and healthy control groups. Accuracy rates between the anal fistula with chronic diarrhea and the chronic diarrhea only groups were 0.9768, 0.909 and 0.964, respectively. Conclusions These results suggest the feasibility of employing serum proteins MIP-1α, MIP-1β and TNF-R1 as potential biomarkers for rapid and convenient diagnosis of anal fistula in chronic diarrhea patients.
Highlights
A fistula is an abnormal opening from inside to outside the body or abnormal tunnel between two or more organs
Expressed proteins were subsequently validated by enzyme-linked immunosorbent assay (ELISA), with a sample population expanded to 30 patients with anal fistulas and chronic diarrhea, 30 patients with chronic diarrheas only and 20 healthy controls
Accuracy rates between the anal fistula with chronic diarrhea and the chronic diarrhea only groups were 0.9768, 0.909 and 0.964, respectively. These results suggest the feasibility of employing serum proteins MIP-1α, MIP-1β and TNF-R1 as potential biomarkers for rapid and convenient diagnosis of anal fistula in chronic diarrhea patients
Summary
A fistula is an abnormal opening from inside to outside the body or abnormal tunnel between two or more organs. Most anal fistulas are idiopathic (approximately 90% of cases) and arise from an injury to the tissue lining the anal canal or an infection and pus formation in that area. Exploration of the anal canal and distal rectum under anesthesia (EUA), performed by experienced surgeons, is the gold standard for assessing an anal fistula [9,10,11], with mandatory rectosigmoidoscopy when assessing perianal disease [9]. This procedure is an unpleasant and invasive
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