Colorectal cancer detection using targeted serum metabolic profiling

Area of Science:

• Biochemistry
• Oncology
• Analytical Chemistry

Background:

• Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally.
• Despite advances in understanding CRC molecular biology, effective biomarkers for early detection and monitoring are still needed.
• Current diagnostic methods for CRC can be invasive or lack sufficient sensitivity and specificity.

Purpose of the Study:

• To develop and validate a targeted metabolic profiling approach for sensitive and specific detection of colorectal cancer (CRC) using human serum.
• To identify potential metabolic biomarkers indicative of CRC presence.
• To assess the diagnostic performance of the developed method in differentiating CRC patients from healthy controls and patients with polyps.

Main Methods:

• Utilized targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) for metabolic profiling.
• Analyzed 158 metabolites across 25 metabolic pathways in serum samples from 234 individuals (66 CRC patients, 76 polyp patients, 92 healthy controls).
• Applied Partial Least-Squares-Discriminant Analysis (PLS-DA) and Receiver Operating Characteristic (ROC) curve analysis for model development and performance evaluation.

Main Results:

• PLS-DA models effectively distinguished CRC patients from healthy controls (AUC=0.93) and polyp patients (AUC=0.95).
• High diagnostic performance was observed with sensitivities of 0.96 (vs. controls) and 0.89 (vs. polyps), and specificities of 0.80 (vs. controls) and 0.88 (vs. polyps).
• Monte Carlo cross-validation confirmed the robustness and diagnostic power of the metabolic profiling approach.

Conclusions:

• Targeted metabolic profiling of human serum is a powerful and non-invasive strategy for colorectal cancer detection.
• The identified metabolic signatures demonstrate significant potential as biomarkers for early CRC screening and diagnosis.
• This approach offers a promising advancement in the field of liquid biopsy for oncological diagnostics.