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.

Figure. 1.

Comparisons of the number of detected peaks between groups. The boxplots display the distributions of the number of detected peaks under pH 10 (left column), pH 7 (middle column), and both (right column) conditions. Group 1 (cases) and 2 (controls) represent colorectal cancer and normal groups. The P-values were estimated by a Mann–Whitney U test (MW test).

Figure. 2.

Score plots of the first and second components. The plot in the left column is for the data generated under pH 10 and that for the data under pH 7 is in the right column. Group 1 (cases) and 2 (controls) represent colorectal cancer and normal groups.