Colorectal cancer and adenoma screening using urinary volatile organic compound (VOC) detection: early results from a single-centre bowel screening population (UK BCSP)

Abstract

Background The United Kingdom (UK) bowel cancer screening programme has reduced mortality from colorectal cancer (CRC), but poor uptake with stool-based tests and lack of specificity of faecal occult blood testing (FOBT), has prompted investigation for a more suitable screening test. The aim of this study was to investigate the feasibility of a urinary volatile organic compounds (VOC)-based screening tool for CRC. Methods The urine from FOBT-positive patients was analysed using field asymmetric ion mobility spectrometry (FAIMS) and gas chromatography coupled with ion mobility spectrometry (GC–IMS). Data were analysed using a machine learning algorithm to calculate the test accuracy for correct classification of CRC against adenomas and other gastrointestinal pathology. Results One hundred and sixty-three patients were enrolled in the study. Test accuracy was high for differentiating CRC from control: area under the curve (AUC) 0.98 (95% CI 0.93–1) and 0.82 (95% CI 0.67–0.97) using FAIMS and GC–IMS respectively. Correct classification of CRC from adenoma was high with AUC range 0.83–0.92 (95% CI 0.43–1.0). Classification of adenoma from control was poor with AUC range 0.54–0.61 (95% CI 0.47–0.75) using both analytical modalities. Conclusions CRC was correctly distinguished from adenomas or no bowel pathology using urinary VOC markers, within the bowel screening population. This pilot study demonstrates the potential of this method for CRC detection, with higher test uptake and superior sensitivity than FOBT. In addition, this is the first application of GC–IMS in CRC detection which has shown high test accuracy and usability. Electronic supplementary material The online version of this article (10.1007/s10151-019-01963-6) contains supplementary material, which is available to authorized users.

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

“…The largest group of increased species were amino acids, represented by i.e., glutamic acid, leucine, serine, valine and phenylalanine. High positive correlations were observed between bacterial species and volatiles, including: Bacteroides , Dialister and Pseudobutyrivibrio —free fatty acids; Ruminococcus —ursodeoxycholic acid; Phascolarctobacterium and Acidiminobacter —phenylalanine and glutamic acid [ 41 ].…”

“…In certain studies, samples from individuals following vegetarian diet or having any dietary restrictions were not included [ 38 , 43 ], as this factor itself could reflect on a differentiated profile of molecules extracted from the collected specimen. Interruption of consumption of tobacco or alcohol was also required in a study [ 41 ]. Song et al, 2018, collected samples provided after overnight fasting and participants were instructed to consume solely local traditional food [ 42 ]; participants enrolled in another study all had a mild diet [ 41 ].…”

“…Interruption of consumption of tobacco or alcohol was also required in a study [ 41 ]. Song et al, 2018, collected samples provided after overnight fasting and participants were instructed to consume solely local traditional food [ 42 ]; participants enrolled in another study all had a mild diet [ 41 ]. Fecal samples were generally provided before the colonoscopy, without the influence of any kind of procedure for bowel preparation [ 38 , 41 , 42 , 43 ].…”

“…Song et al, 2018, collected samples provided after overnight fasting and participants were instructed to consume solely local traditional food [ 42 ]; participants enrolled in another study all had a mild diet [ 41 ]. Fecal samples were generally provided before the colonoscopy, without the influence of any kind of procedure for bowel preparation [ 38 , 41 , 42 , 43 ]. Another common exclusion criteria regards the intake of antibiotics and probiotics months prior to sample donation, once these agents impact the natural composition of gut microbiota [ 41 , 43 ].…”

“…Fecal samples were generally provided before the colonoscopy, without the influence of any kind of procedure for bowel preparation [ 38 , 41 , 42 , 43 ]. Another common exclusion criteria regards the intake of antibiotics and probiotics months prior to sample donation, once these agents impact the natural composition of gut microbiota [ 41 , 43 ]. In most of the studies, patients suffering from intestinal chronic inflammatory diseases were also not enrolled [ 38 , 39 , 41 , 43 ], due to the possibility that the metabolic alterations promoted by these conditions may result in a false positive or a confounding factor when CRC cases are evaluated.…”