Large-scale targeted metabolomics method for metabolite profiling of human samples

Area of Science:

• Metabolomics
• Biochemistry
• Analytical Chemistry

Background:

• Targeted metabolomics offers quantification but limited metabolite coverage.
• Unbiased metabolite identification is crucial for expanding metabolomic analysis.

Purpose of the Study:

• Develop a large-scale targeted metabolomics method for diverse human samples.
• Enhance metabolite coverage and analytical performance compared to existing methods.
• Apply the method for biomarker discovery in lung cancer.

Main Methods:

• Utilized ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution Orbitrap mass spectrometry (MS) for initial metabolite identification.
• Established a targeted metabolomics method using UHPLC-triple quadrupole MS for profiling over 400 metabolites across 92 metabolic pathways.
• Validated method performance in human cells, tissues, and body fluids.

Main Results:

• The developed method profiles >400 metabolites in 92 pathways with high sensitivity, repeatability, and linearity.
• Successfully identified 107 differential metabolites distinguishing lung cancer from normal tissues.
• Results implicate the Warburg effect, altered redox state, and nucleotide metabolism in lung cancer.

Conclusions:

• The new large-scale targeted metabolomics method provides wide metabolite coverage and excellent analytical performance.
• Demonstrates significant utility and flexibility for biomarker discovery in clinical and basic research.
• Offers advantages over untargeted metabolomics for sensitive and reproducible quantification.