An exploratory serum metabolomics study for screening and staging of breast cancer.

[OBJECTIVE] This study investigates serum metabolic profiles in breast cancer to identify diagnostic biomarkers and stage-specific metabolites, offering insights for clinical practice.

[METHODS] Gas chromatography‒mass spectrometry (GC‒MS)-based metabolomics analyzed serum from healthy controls, patients with benign breast lesions, and malignant breast cancer cohorts. Orthogonal partial least squares discriminant analysis (OPLS-DA) modeling differentiated metabolic signatures between groups, while Spearman's correlation assessed metabolite-stage relationships. Diagnostic performance was assessed through receiver operating characteristic (ROC) analysis.

[RESULTS] Amino acid metabolism alterations, particularly in alanine, aspartate, and glutamate metabolism, characterized breast cancer. Malignant cases showed elevated glutamic acid and lactic acid but reduced fructose compared to benign lesions, achieving significant diagnostic discrimination (AUC = 0.9757 for glutamic acid, AUC = 0.9583 for lactic acid, AUC = 1.000 for fructose). Glutamic acid demonstrated progressive elevation across health-to-disease continuum (healthy-benign-early-stage-advanced), strongly correlating with the malignancy stage ( = 0.934,  < 0.001) and effectively distinguishing early/late-stage cancers (AUC = 0.9500).

[CONCLUSIONS] Serum metabolomics identified glutamic acid as a dynamic biomarker for breast cancer detection and staging, warranting further mechanistic studies.