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

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 cuttingedge GC x 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 mu L serum) and metabolomics (50 mu L 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 (omega-3) molecules are inversely associated with increased odds of CRC, while some PUFA (omega-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.

Automated summary

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths. Current diagnostic techniques are either invasive or lack sensitivity, highlighting the need for less invasive and more sensitive screening approaches. This study used advanced GC x GC-LR/HR-TOFMS technology to analyze serum samples from three different groups (adenocarcinoma, adenoma, and control). The findings revealed specific PUFA molecules inversely associated with CRC and identified metabolic changes in CRC. The study provides valuable insight into molecular-level changes associated with CRC and compares the efficiency of different analytical approaches for CRC screening.