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Global Plasma Profiling for Colorectal Cancer-Associated Volatile Organic Compounds: a Proof-of-Principle Study.

ABSTRACT: Volatile organic compounds (VOCs) could reflect changes resulting from ongoing pathophysiological processes and altered body metabolisms, and thus have been studied for various types of cancers. We aimed to test an advanced global metabolomic technique to characterize circulating VOCs in patients diagnosed with colorectal cancer (CRC). We employed solid-phase microextraction (SPME) and comprehensive two-dimensional gas chromatography mass-spectrometry (GC × GC-MS). We analyzed 30 random plasma samples from incident cases of CRC. The 30 samples were from population controls enrolled in a large population-based case-control study. The number of metabolite peaks detected in the cases was significantly lower than that detected in the controls (median 1530 vs. 1694, P = 0.02). Partial least squares-discriminant analysis showed clear VOC profile differences between the CRC and the controls. After adjustment for multiple comparisons at the 5% false discovery rate level, five VOCs were differentially expressed between the cases and the controls. Among these five VOCs, 2,3,4-trimethyl-hexane (decreased) and 2,4-dimethylhept-1-ene (increased) were both lipid peroxidation products but not previously reported for CRC. In summary, this study pointed to an intriguing observation that the richness of volatile metabolites may be reduced in CRC cases and demonstrated the utility of SPME GC × GC-MS in discovery of candidate markers for further validation.

SUBMITTER: Kim S

PROVIDER: S-EPMC6478127 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Global Plasma Profiling for Colorectal Cancer-Associated Volatile Organic Compounds: a Proof-of-Principle Study.

Kim Seongho S Yin Xinmin X Prodhan Md Aminul Islam MAI Zhang Xiang X Zhong Zichun Z Kato Ikuko I

Journal of chromatographic science 20190501 5

Volatile organic compounds (VOCs) could reflect changes resulting from ongoing pathophysiological processes and altered body metabolisms, and thus have been studied for various types of cancers. We aimed to test an advanced global metabolomic technique to characterize circulating VOCs in patients diagnosed with colorectal cancer (CRC). We employed solid-phase microextraction (SPME) and comprehensive two-dimensional gas chromatography mass-spectrometry (GC × GC-MS). We analyzed 30 random plasma s ...[more]

PMID: 30796770

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Project description:BackgroundColorectal cancer remains a leading cause of mortality and morbidity. The UK Bowel Cancer Screening Programme (BCSP) has demonstrated that detection of colorectal cancer at an earlier stage and identification of advanced pre-malignant adenomas reduces mortality and morbidity.AimTo assess the utility of volatile organic compounds as a biomarker for colorectal neoplasia.MethodsFaeces were collected from symptomatic patients and people participating in the UK BCSP, prior to colonoscopy. Headspace extraction followed by gas chromatography mass spectrometry was performed on faeces to identify volatile organic compounds. Logistic regression modelling and 10-fold cross-validation were used to test potential biomarkers.ResultsOne hundred and thirty-seven participants were included (mean age 64 years [range 22-85], 54% were male): 60 had no neoplasia, 56 had adenomatous polyp(s) and 21 had adenocarcinoma. Propan-2-ol was significantly more abundant in the cancer samples (P < 0.0001, q = 0.004) with an area under ROC (AUROC) curve of 0.76. When combined with 3-methylbutanoic acid the AUROC curve was 0.82, sensitivity 87.9% (95% CI 0.87-0.99) and specificity 84.6% (95% CI 0.65-1.0). Logistic regression analysis using the presence/absence of specific volatile organic compounds, identified a three volatile organic compound panel (propan-2-ol, hexan-2-one and ethyl 3-methyl- butanoate) to have an AUROC of 0.73, with a person six times more likely to have cancer if all three volatile organic compounds were present (P < 0.0001).ConclusionsVolatile organic compound analysis may have a superior diagnostic ability for the identification of colorectal adenocarcinoma, when compared to other faecal biomarkers, including those currently employed in UK. Clinical trial details: National Research Ethics Service Committee South West - Central Bristol (REC reference 14/SW/1162) with R&D approval from University of Liverpool and Broadgreen University Hospital Trust (UoL 001098).

Dataset Information

Global Plasma Profiling for Colorectal Cancer-Associated Volatile Organic Compounds: a Proof-of-Principle Study.

Publications

Global Plasma Profiling for Colorectal Cancer-Associated Volatile Organic Compounds: a Proof-of-Principle Study.

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