Volatile organic compounds emitted from faeces as a biomarker for colorectal cancer

Abstract

Summary Background Colorectal cancer remains a leading cause of mortality and morbidity. The UK Bowel Cancer Screening Programme (BCSP) has demonstrated that detection of colorectal cancer at an earlier stage and identification of advanced pre‐malignant adenomas reduces mortality and morbidity. Aim To assess the utility of volatile organic compounds as a biomarker for colorectal neoplasia. Methods Faeces were collected from symptomatic patients and people participating in the UK BCSP, prior to colonoscopy. Headspace extraction followed by gas chromatography mass spectrometry was performed on faeces to identify volatile organic compounds. Logistic regression modelling and 10‐fold cross‐validation were used to test potential biomarkers. Results One hundred and thirty‐seven participants were included (mean age 64 years [range 22‐85], 54% were male): 60 had no neoplasia, 56 had adenomatous polyp(s) and 21 had adenocarcinoma. Propan‐2‐ol was significantly more abundant in the cancer samples (P < 0.0001, q = 0.004) with an area under ROC (AUROC) curve of 0.76. When combined with 3‐methylbutanoic acid the AUROC curve was 0.82, sensitivity 87.9% (95% CI 0.87‐0.99) and specificity 84.6% (95% CI 0.65‐1.0). Logistic regression analysis using the presence/absence of specific volatile organic compounds, identified a three volatile organic compound panel (propan‐2‐ol, hexan‐2‐one and ethyl 3‐methyl‐ butanoate) to have an AUROC of 0.73, with a person six times more likely to have cancer if all three volatile organic compounds were present (P < 0.0001). Conclusions Volatile organic compound analysis may have a superior diagnostic ability for the identification of colorectal adenocarcinoma, when compared to other faecal biomarkers, including those currently employed in UK. Clinical trial details: National Research Ethics Service Committee South West ‐ Central Bristol (REC reference 14/SW/1162) with R&D approval from University of Liverpool and Broadgreen University Hospital Trust (UoL 001098).

Editorial: metabolomic biomarkers for colorectal adenocarcinoma and in the differentiation between irritable bowel syndrome and ulcerative colitis in clinical remission — confounded by the gut microbiome? Authors' reply

“…We welcome the interest expressed by Leong et al in our work looking at metabolomics biomarkers for gastrointestinal disease . We have previously reported the volatile organic compounds emitted from faecal samples in patients with irritable bowel syndrome, Crohn's disease, ulcerative colitis and asymptomatic controls using headspace gas chromatography mass spectrometry, and also using a gas chromatography‐sensor system .…”

“…The editorial accompanies our latest study which has reported the association between a small group of faecal volatile organic compounds and the presence of colorectal adenocarcinoma . Propan‐2‐ol (also known as isopropanol) was significantly more abundant in the cancer samples than controls ( P < 0.0001, q = 0.004).…”

A Review of GC-Based Analysis of Non-Invasive Biomarkers of Colorectal Cancer and Related Pathways

“…The selected model provided correct classification of 14 patients with polyps over 15 for the group of patients with colorectal cancer, with a sensitivity of 93.3%. Group with polyps were distinguished as markedly pathological [ 48 ].…”

Editorial: metabolomic biomarkers for colorectal adenocarcinoma and in the differentiation between irritable bowel syndrome and ulcerative colitis in clinical remission—confounded by the gut microbiome?

“…In gastrointestinal diseases, faecal and urinary samples are ideal sources of metabolic signatures of divergent pathogenic pathways; the noninvasive nature of their collection makes them fitting for novel diagnostics. Two recent publications in AP&T aimed to identify molecules that accurately diagnose gastrointestinal diseases based on metabolic profiling.…”

“…Using Headspace GCMS to define profiles of volatile organic compounds (VOCs) in faeces, Bond et al were able to accurately differentiate patients with colorectal adenocarcinoma from controls by summation of three compounds (AUROC 0.73). Propan‐2‐ol was the strongest single biomarker with an AUROC to predict adenocarcinoma of 0.76.…”