Detection of Colorectal Cancer (CRC) by Urinary Volatile Organic Compound Analysis
尿液揮發性有機物分析檢測結直腸癌（CRC）
Ramesh P. Arasaradnam1,3*, Michael J. McFarlane3, Courtenay Ryan-Fisher3, Erik Westenbrink2,
Paula Hodges3, Matthew G. Thomas2,6, Samantha Chambers3, Nicola O’Connell3, Catherine Bailey3,
Christopher Harmston5, Chuka U. Nwokolo3, Karna D. Bardhan1,4, James A. Covington2
1 Clinical Sciences Research Institute, University of Warwick, Coventry, Warwickshire, United Kingdom,
2 School of Engineering, University of Warwick, Coventry,Warwickshire, United Kingdom,
3 Department of Gastroenterology, University Hospital Coventry & Warwickshire, Coventry, Warwickshire, United Kingdom,
4 Departmentof Gastroenterology, Rotherham General Hospital, Rotherham, Yorkshire, United Kingdom,
5 Department of Surgery, University Hospital Coventry and Warwickshire,Coventry, Warwickshire, United Kingdom,
6 MOAC Doctoral Training Centre, University of Warwick, Coventry, Warwickshire, United Kingdom
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 Guaiac based faecal occult blood (gFOB) testing has largely been superseded by Faecal Immunochemical testing (FIT), but sensitivity still remains poor.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.
結直腸癌(CRC)是歐美腫瘤相關死亡的主要原因，目前尚無*的有效的無創性CRC篩查方法。以愈創木酚為基礎的糞便隱血(gFOB)檢測已基本被糞便免疫化學檢測(FIT)所取代，但敏感性仍然很差。在英國，基于人群的FOBt檢測的普及率也很低，只有50%左右。使用各種氣相分析儀器檢測多種癌癥亞型的揮發性有機化合物(VOCs)特征越來越受到關注。其中一個例子是場非對稱離子遷移率譜儀(FAIMS)。FAIMS能夠通過分析尿液和糞便中VOCs模式的變化來識別炎癥性腸病(IBD)患者。這項研究擴展了這一概念，以確定是否可以通過非侵入性分析尿液，使用FAIMS結直腸癌患者。共招募133名患者，83名大腸癌患者和50名健康對照者。采用FAIMS儀器(Owlstone，lonestar，UK公司)進行CRC診斷和頂空分析時收集尿液。從原始數據中提取特征后，使用fisher判別分析(fda)對數據進行處理。FAIMS分析表明，CRC患者的VOC譜是緊密聚集的，可以與健康對照組區分開來。FAIMS檢測CRC的敏感性為88%，特異性為60%。這項研究表明，利用離子遷移譜技術(FAIMS)可以檢測出CRC患者尿液中的VOC信號，這可能是一種新的篩查手段
