Comprehensive Insight into Colorectal Cancer Metabolites and Lipids for Human Serum: A Proof-of-Concept Study

Int J Mol Sci. 2023 Jun 1;24(11):9614. doi: 10.3390/ijms24119614.

Abstract

Colorectal cancer (CRC) ranks as the third most frequently diagnosed cancer and the second leading cause of cancer-related deaths. The current endoscopic-based or stool-based diagnostic techniques are either highly invasive or lack sufficient sensitivity. Thus, there is a need for less invasive and more sensitive screening approaches. We, therefore, conducted a study on 64 human serum samples representing three different groups (adenocarcinoma, adenoma, and control) using cutting-edge GC×GC-LR/HR-TOFMS (comprehensive two-dimensional gas chromatography coupled with low/high-resolution time-of-flight mass spectrometry). We analyzed samples with two different specifically tailored sample preparation approaches for lipidomics (fatty acids) (25 μL serum) and metabolomics (50 μL serum). In-depth chemometric screening with supervised and unsupervised approaches and metabolic pathway analysis were applied to both datasets. A lipidomics study revealed that specific PUFA (ω-3) molecules are inversely associated with increased odds of CRC, while some PUFA (ω-6) analytes show a positive correlation. The metabolomics approach revealed downregulation of amino acids (alanine, glutamate, methionine, threonine, tyrosine, and valine) and myo-inositol in CRC, while 3-hydroxybutyrate levels were increased. This unique study provides comprehensive insight into molecular-level changes associated with CRC and allows for a comparison of the efficiency of two different analytical approaches for CRC screening using same serum samples and single instrumentation.

Keywords: GC×GC–TOFMS; blood; chemometrics; colorectal cancer; comprehensive gas chromatography; lipidomics; mass spectrometry; metabolomics; sample preparation; separation science; serum.

MeSH terms

  • Colorectal Neoplasms* / diagnosis
  • Fatty Acids
  • Gas Chromatography-Mass Spectrometry / methods
  • Humans
  • Mass Spectrometry / methods
  • Metabolomics* / methods

Substances

  • Fatty Acids