粪便挥发性有机化合物用于检测林奇综合征中的结直肠肿瘤——一项前瞻性纵向多中心研究
Faecal Volatile Organic Compounds to Detect Colorectal Neoplasia in Lynch Syndrome-A Prospective Longitudinal Multicentre Study.
作者信息
van Liere Elsa L S A, Ramsoekh Dewkoemar, Daulton Emma, Dakkak Maya, van Lingen Joris M, Stewart Trenton K, Bosch Sofie, Carvalho Beatriz, Dekker Evelien, Jacobs Maarten A J M, Koornstra Jan Jacob, Kuijvenhoven Johan P, van Leerdam Monique E, de Meij Tim G J, Meijer Gerrit A, Spaander Manon C W, Covington James A, de Boer Nanne K H
机构信息
Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam, The Netherlands.
出版信息
Aliment Pharmacol Ther. 2025 Jan;61(1):145-158. doi: 10.1111/apt.18328. Epub 2024 Oct 18.
BACKGROUND
Non-invasive biomarkers may reduce post-colonoscopy colorectal cancer (CRC) rates and colonoscopy overuse in Lynch syndrome. Unlike faecal immunochemical test (FIT), faecal volatile organic compounds (VOCs) may accurately detect both advanced and non-advanced colorectal neoplasia.
AIM
The aim of this study was to evaluate the potential of faecal VOCs-separately and with FIT-to guide optimal colonoscopy intervals in Lynch syndrome.
METHODS
Prospective longitudinal multicentre study in which individuals with Lynch syndrome collected faeces before and after high-quality surveillance colonoscopy. VOC-patterns were analysed using field asymmetric ion mobility spectrometry (FAIMS) and gas chromatography-ion mobility spectrometry (GC-IMS) followed by machine learning pipelines, and combined with FIT at 2.55 μg Hb/g faeces. Gas chromatography time-of-flight mass spectrometry analysed individual VOC abundance.
RESULTS
Among 200 included individuals (57% female, median 51 years), 62 had relevant neoplasia at colonoscopy: 3 CRC, 6 advanced adenoma (AA), 3 advanced serrated lesion (ASL), and 50 non-advanced adenoma (NAA). Respective sensitivity and negative predictive value for CRC and AA (and also ASL in case of FAIMS) were 100% and 100% using FAIMS (54% specificity), and 89% and 99% using GC-IMS (58% specificity). Respective sensitivity and specificity for any relevant neoplasia were 88% and 44% (FAIMS) and 84% and 28% (GC-IMS); accuracy did not significantly improve upon VOC-FIT. VOC-patterns differed before and after polypectomy (AUC 0.70). NAA showed decreased faecal abundance of butanal, 2-oxohexane, dimethyldisulphide and dimethyltrisulphide.
CONCLUSIONS
In Lynch syndrome, faecal VOCs may be a promising strategy for postponing colonoscopy and for follow-up after polypectomy. Our results serve as a stepping stone for large validation studies.
TRIAL REGISTRATION
NL8749.
背景
非侵入性生物标志物可能降低林奇综合征患者结肠镜检查后结直肠癌（CRC）的发生率，并减少结肠镜检查的过度使用。与粪便免疫化学检测（FIT）不同，粪便挥发性有机化合物（VOCs）可能准确检测进展期和非进展期结直肠肿瘤。
目的
本研究的目的是评估粪便VOCs单独使用以及与FIT联合使用，以指导林奇综合征患者最佳结肠镜检查间隔时间的潜力。
方法
一项前瞻性纵向多中心研究，林奇综合征患者在高质量监测结肠镜检查前后收集粪便。使用场不对称离子迁移谱（FAIMS）和气相色谱-离子迁移谱（GC-IMS）分析VOC模式，随后采用机器学习流程，并与粪便血红蛋白浓度为2.55μg/g时的FIT结果相结合。气相色谱飞行时间质谱分析个体VOC丰度。
结果
在纳入的200名个体中（57%为女性，中位年龄51岁），62人在结肠镜检查时有相关肿瘤：3例CRC、6例进展性腺瘤（AA）、3例进展性锯齿状病变（ASL）和50例非进展性腺瘤（NAA）。使用FAIMS（特异性54%）时，CRC和AA（FAIMS检测ASL时也是如此）的敏感性和阴性预测值分别为100%和100%，使用GC-IMS（特异性58%）时分别为89%和99%。任何相关肿瘤的敏感性和特异性分别为88%和44%（FAIMS）以及84%和28%（GC-IMS）；VOC-FIT联合检测的准确性没有显著提高。息肉切除前后的VOC模式不同（曲线下面积为0.70）。NAA显示粪便中丁醛、2-氧代己烷、二甲基二硫和二甲基三硫的丰度降低。
结论
在林奇综合征中，粪便VOCs可能是推迟结肠镜检查和息肉切除术后随访的一种有前景的策略。我们的结果为大型验证研究奠定了基础。
试验注册号
NL8749。
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