Identification of Potential Biomarkers for Breast Cancer Based on Salivary Metabolomics

Introduction: Breast cancer (BC) remains the most prevalent malignant tumor in women worldwide and a leading cause of cancer-related mortality. Early screening is essential to improve prognosis, yet current diagnostic methods are often invasive or lack sensitivity. Saliva is an accessible and non-invasive biofluid containing various metabolites that reflect systemic physiological and pathological changes. Thus, salivary metabolomics may provide novel insights into breast cancer-associated metabolic alterations and support the development of early diagnostic strategies. Objectives To explore the salivary metabolomic profile of breast cancer patients and identify potential non-invasive biomarkers for early breast cancer screening. Methods Saliva samples were collected from 30 breast cancer patients and 20 healthy controls. An untargeted metabolomics approach was applied using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Multivariate analyses (PCA, OPLS-DA), KEGG pathway enrichment, and ROC curve analysis were used to characterize metabolic differences and evaluate the diagnostic performance of candidate biomarkers. Results A total of 101 differential metabolites were identified, including 81 upregulated and 20 downregulated compounds. Significant alterations were observed in caffeine metabolism, choline metabolism, and amino acid metabolism pathways. Among them, 2-aminonicotinic acid and theobromine demonstrated moderate diagnostic value, with AUCs of 0.82 and 0.85, respectively. However, diagnostic thresholds and confidence intervals require further validation in larger cohorts. Conclusion The salivary metabolome of breast cancer patients displays distinct changes compared to healthy individuals. These metabolic alterations suggest disruptions in energy metabolism, oxidative stress response, and immune regulation in breast cancer. Salivary metabolites such as 2-aminonicotinic acid and theobromine may serve as promising non-invasive biomarkers, although further studies are needed to confirm their diagnostic utility and specificity.