Use of the Analysis of the Volatile Faecal Metabolome in Screening for Colorectal Cancer

Abstract

Diagnosis of colorectal cancer is an invasive and expensive colonoscopy, which is usually carried out after a positive screening test. Unfortunately, existing screening tests lack specificity and sensitivity, hence many unnecessary colonoscopies are performed. Here we report on a potential new screening test for colorectal cancer based on the analysis of volatile organic compounds (VOCs) in the headspace of faecal samples. Faecal samples were obtained from subjects who had a positive faecal occult blood sample (FOBT). Subjects subsequently had colonoscopies performed to classify them into low risk (non-cancer) and high risk (colorectal cancer) groups. Volatile organic compounds were analysed by selected ion flow tube mass spectrometry (SIFT-MS) and then data were analysed using both univariate and multivariate statistical methods. Ions most likely from hydrogen sulphide, dimethyl sulphide and dimethyl disulphide are statistically significantly higher in samples from high risk rather than low risk subjects. Results using multivariate methods show that the test gives a correct classification of 75% with 78% specificity and 72% sensitivity on FOBT positive samples, offering a potentially effective alternative to FOBT.

Volatile organic compounds as new biomarkers for colorectal cancer: a review

“…Batty et al . studied 31 faecal samples from normal controls and 31 from a group of high‐risk patients with a high grade adenoma or adenocarcinoma, stratified after colonoscopy performed on the basis of positivity on a faecal occult blood test. SIFT‐MS analysis was performed using each of the three precursor ions available (H 3 O + , NO + , O 2 + ).…”

“…After removal of duplicates and screening for relevant titles, 10 articles were submitted for a full-text analysis and included in this systematic review. Three were related to VOC identified in urine [16][17][18], four in exhaled breath [8,[19][20][21], one in blood [22] and two in faeces [23,24] using different analytical platforms.…”

“…, probably because of the different procedures employed in collection and analysis of the samples . So far only one study has focused on the monitoring of VOC from blood samples and two from faeces , and both studies had small sample sizes. These studies should therefore be considered as only preliminary.…”

Application of Fecal Volatile Organic Compound Analysis in Clinical Practice: Current State and Future Perspectives

“…They found that both patients with CRC and AA could be discriminated from controls (Table 3). In a second study, fecal VOC profiles of patients with a positive fecal occult blood test (FOBT) were assessed by means of SIFT-MS [50]. By colonoscopy, patients were classified into risk groups (e.g., low risk and high risk) based on their histopathology.…”

Molecular Biomarkers of Colorectal Cancer and Cancer Disparities: Current Status and Perspective

“…Overall, the pool of metabolites found to be distinct between normal and CRC patients included (a) 3-hydroxybutyric acid, L-valine, L-threonine, 1-deoxyglucose, and glycine [141]; (b) a panel consisting of citrate, hippurate, p -cresol, 2-aminobutyrate, myristate, putrescine, and kynurenate [142]; (c) alanine, citrate, creatine, glutamine, peptide NHs, lactate, leucine, pyruvate, tyrosine, 3-hydroxybutyrate, acetate, formate, glycerol, lipid (−CH 2 –OCOR), the N-acetyl signal of glycoproteins, phenylalanine, and proline [143]; (d) hydroxylated polyunsaturated ultra long-chain fatty acid metabolites [144]; (e) glucose, inositol, hypoxanthine, xanthine, uric acid, and deoxycholic acid [145]; (f) L-valine, 5-oxo-L-proline, 1-deoxyglucose, D-turanose, D-maltose, arachidonic acid, hexadecanoic acid, and L-tyrosine [146]; (g) proline, cysteine, acetate, and butyrate [147]; and (h) L-alanine, glucuronic lactone, and L-glutamine [148]. Most of these metabolites are yet to be validated but might serve as tools for the early detection, prediction, and prognosis of CRC [149–152]. …”