Department of Gastroenterology, University Hospitals Coventry and Warwickshire, Coventry, UK.
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
Colorectal Dis. 2019 Nov;21(11):1259-1269. doi: 10.1111/codi.14739. Epub 2019 Jul 10.
Volatile organic compounds (VOCs) are potential biomarkers for diagnosing colorectal cancer (CRC). We characterized urinary VOCs from CRC patients, their spouses/cohabitors (spouses) and first-degree relatives (relatives) to determine any differences. Correlation with stool-derived microbiomes was also undertaken.
Urine from 56 CRC patients, 45 spouses and 37 relatives was assayed using liquid chromatography, field asymmetric ion mobility spectrometry (FAIMS), mass spectrometer technology. Analysis was performed using five-fold cross-validation and a random forest classifier. Faecal microbiome 16S rRNA was sequenced using Illumina MiSeq protocols and analysed using UPARSE and QIIME pipelines. VOC and microbiome profiles were also compared before and after cancer treatment.
Urinary VOC profiles of CRC patients were indistinguishable from either spouses or relatives. When spouses and relatives were grouped together to form a larger non-cancer control group (n = 82), their VOC profiles became distinguishable from those of CRC patients (n = 56) with 69% sensitivity and specificity, area under the curve 0.72 (P < 0.001). Microbiome analysis identified > 1300 operational taxonomic units across all groups. The analysis of similarity R value was 0.067 (P < 0.001), with significantly different bacterial abundances in 82 operational taxonomic units (6.2%) by Kruskal-Wallis testing. CRC patients' VOC or stool microbiome profiles were unchanged after treatment.
Although CRC patients' urinary VOC profiles cannot be differentiated from those of spouses or relatives they can be differentiated from a larger non-cancer control group. Comparison of the groups' microbiomes confirmed differences in bacterial species abundance. The current FAIMS-based assay can detect a unique, but modest, signal in CRC patients' urinary VOCs, which remains unaltered after treatment.
挥发性有机化合物(VOCs)是诊断结直肠癌(CRC)的潜在生物标志物。我们对 CRC 患者、配偶/同居者(配偶)和一级亲属(亲属)的尿液 VOCs 进行了特征分析,以确定任何差异。还进行了与粪便衍生微生物组的相关性研究。
使用液相色谱法、场不对称离子迁移谱(FAIMS)、质谱仪技术对 56 名 CRC 患者、45 名配偶和 37 名亲属的尿液进行了检测。分析采用五重交叉验证和随机森林分类器进行。使用 Illumina MiSeq 方案对粪便微生物组 16S rRNA 进行测序,并使用 UPARSE 和 QIIME 进行分析。还比较了癌症治疗前后的 VOC 和微生物组谱。
CRC 患者的尿液 VOC 谱与配偶或亲属无法区分。当将配偶和亲属归为一组形成更大的非癌症对照组(n=82)时,他们的 VOC 谱与 56 名 CRC 患者(n=56)的谱变得可区分,具有 69%的敏感性和特异性,曲线下面积为 0.72(P<0.001)。微生物组分析在所有组中鉴定出了>1300 个操作分类单位。分析相似性 R 值为 0.067(P<0.001),Kruskal-Wallis 检验显示 82 个操作分类单元中有 6.2%的细菌丰度存在显著差异。CRC 患者治疗后其尿液 VOC 或粪便微生物组谱未发生变化。
尽管 CRC 患者的尿液 VOC 谱与配偶或亲属无法区分,但可以与更大的非癌症对照组区分开。对这些组的微生物组的比较证实了细菌物种丰度的差异。目前基于 FAIMS 的检测方法可以检测到 CRC 患者尿液 VOC 中独特但适度的信号,且治疗后未发生改变。