Detection of Colorectal Cancer (CRC) by Urinary Volatile Organic Compound Analysis

Abstract

Colorectal cancer (CRC) is a leading cause of cancer related death in Europe and the USA. There is no universally accepted effective non-invasive screening test for CRC. Guaiac based faecal occult blood (gFOB) testing has largely been superseded by Faecal Immunochemical testing (FIT), but sensitivity still remains poor. The uptake of population based FOBt testing in the UK is also low at around 50%. The detection of volatile organic compounds (VOCs) signature(s) for many cancer subtypes is receiving increasing interest using a variety of gas phase analytical instruments. One such example is FAIMS (Field Asymmetric Ion Mobility Spectrometer). FAIMS is able to identify Inflammatory Bowel disease (IBD) patients by analysing shifts in VOCs patterns in both urine and faeces. This study extends this concept to determine whether CRC patients can be identified through non-invasive analysis of urine, using FAIMS. 133 patients were recruited; 83 CRC patients and 50 healthy controls. Urine was collected at the time of CRC diagnosis and headspace analysis undertaken using a FAIMS instrument (Owlstone, Lonestar, UK). Data was processed using Fisher Discriminant Analysis (FDA) after feature extraction from the raw data. FAIMS analyses demonstrated that the VOC profiles of CRC patients were tightly clustered and could be distinguished from healthy controls. Sensitivity and specificity for CRC detection with FAIMS were 88% and 60% respectively. This study suggests that VOC signatures emanating from urine can be detected in patients with CRC using ion mobility spectroscopy technology (FAIMS) with potential as a novel screening tool.

Non-Invasive Distinction of Non-Alcoholic Fatty Liver Disease using Urinary Volatile Organic Compound Analysis: Early Results

“…This suggests that there may be a discernible VOC profile for the various stages of NAFLD. Within this pilot study we have not controlled for age or sex but in our previous work neither of these variables affected VOC profiling [20][21][22][23][24]. All diabetic patients were excluded and only stable cirrhotic patients were included, none of whom were receiving or had recently received any antibiotics.…”

“…The Random Forest algorithm (implemented in the R package 'randomForest' , version 4.6-10, R version 3.1.1) (http://cran.ro-project.org/web/ packages/randomForest/index.html) was applied inside the cross-validation loop. From previous studies we have shown that Random Forest provides the best performance for these types of datasets and this was applied here [20][21][22][23][24]. …”

“…Analysis of urinary VOCs has also distinguished colorectal cancer from healthy controls using FAIMS (Field Asymmetric Ion Mobility Spectrometry) technology [20]. VOC patterns in urine have been analyzed by E-nose (Electronic nose) and also FAIMS (a type of E-nose), to distinguish between not only Inflammatory Bowel Disease (IBD) and healthy controls but between active and quiescent disease for both IBD subtypes [21].…”

Recent Applications of Electronic-Nose Technologies for the Noninvasive Early Diagnosis of Gastrointestinal Diseases

“…Compared with SIFT-MS, FAIM operates at a fraction of the cost (10-20%) of SIFT-MS, although SIFT-MS outperforms the diagnostic power of SIFT-MS [19]. Detection of colorectal cancer (CRC) recently was achieved by FAIMS-analysis of headspace urinary VOC signatures using Fisher discriminant analysis [20]. FAIMS also was used to differentiate diagnoses of patients with coeliac disease (CD) from IBD by sparse logistic regression analysis of headspace urinary VOCs and the discovery of a single disease biomarker (1,3,5,7-cyclooctatetraene), identified by GC-MS in CD-urine VOCs, which was absent in urine from IBD patients [21].…”

Non-Invasive Detection of Anastomotic Leakage Following Esophageal and Pancreatic Surgery by Urinary Analysis

“…These compounds have several origins: firstly, environmental or exogenous; secondly, local symptoms from the ­primary affected disease site in diseased patients which is often inflammation or cancer; and thirdly, the systemic (immunological) response [8]. Assessment of VOCs in breath, feces, and urine has led to the identification of a variety of disease-specific smell prints in, for example, pulmonology, oncology, and gastroenterology [9-14]. …”