Non-invasive biomarkers for early oral cancer detection through multiomics approach

Non-invasive biomarker-based approaches are urgently needed to support early identification and monitoring of Oral squamous cell carcinoma (OSCC) and its precursor, oral submucous fibrosis (OSMF).

We employed combined metabolomic and proteomic analyses to profile saliva and lesion surface swabs from clinically diagnosed OSCC (n = 15), OSMF (n = 20), and healthy controls (n = 27). Polar and nonpolar metabolites were extracted separately from saliva, while proteins were isolated from exfoliated mucosal epithelial cells. Differential expression, pathway enrichment, and biomarker classification were performed across four comparisons: OSCC vs non-OSCC (controls + OSMF), OSCC vs OSMF, OSMF vs control, and OSCC vs control.

Distinct molecular changes were observed across the health-to-cancer spectrum. Top discriminatory salivary metabolites included linoelaidic acid, gamma-glutamylcysteine, and 3-hydroxybutyryl-CoA, implicating dysregulated linoleic acid metabolism, redox imbalance, and fatty acid β-oxidation in pathogenesis. Proteomic data revealed significant upregulation of histone variants, cytoskeletal keratins, and BPI-fold-containing proteins in OSCC, reflecting chromatin remodelling and epithelial-mesenchymal transition. Multivariate biomarker panels achieved high accuracy (AUC ≥ 0.96) for classifying OSMF from OSCC.

Our combined metabolomic and proteomic profiling revealed non-invasive molecular signatures for early detection and monitoring of OSCC and OSMF.