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

Abstract

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).

Figure 1

Partial least square discriminate analysis comparing those with adenocarcinoma of the colon (red) and no colonic neoplasia (green)

Figure 2

Box plots to show the relative abundance of propan‐2‐ol in faeces from all participants. All patients in each cohort are included Normal (no neoplasia) n = 60, adenoma n = 56 and cancer n = 21

Figure 3

Receiver operating characteristic curve for propan‐2‐ol when comparing those with adenocarcinoma of the colon and no colonic neoplasia

Figure 4

Partial least square discriminate analysis using all the identified VOCs, comparing those with no neoplasia against those with > 4 individual polyps of any size