Metabolomics-Based Discovery of Biomarkers for Oral Squamous Cell Carcinoma and Their Clinical Utility

Abstract

The most common pathological type of the oral malignancies is oral squamous cell carcinoma (OSCC). Most patients visit the doctor when they notice signs like pain, ulceration, or dysphagia, and as such, patients have not been identified as soon as possible and recurrence and lymph node metastasis have formed the basis of survival. Metabolomics, which concentrates on small-molecule metabolites, has the potential to generate comprehensive >single cell-type phenotypic readout of tumor cell metabolic reorganization, host immune reactions, nutrition, and microecological disturbances on biofluids and tissues, thereby providing translatable leads in noninvasive screening, risk stratification, and longitudinal follow-up herein OSCC. As a strategy, this article consists of synthizing available evidence as well as systematically re-presenting resources of published findings, providing the discovery pathway of OSCC metabolic biomarkers based on sample types (plasma/serum/saliva/tissue), analytical platforms (NMR and mass spectrometry) and statistical modeling (multivariate discrimination and targeted validation). Quantitative findings directly presented in three published papers are compiled into re-usable graphical evidence: subgroup effects on ROC performance (AUC, sensitivity, specificity) of a plasma multivariate model based on NMR; monotonic fluctuations of key serum metabolites between stages I and IV (Lu et al., 2025); AUC ranking of various biomarkers of selected metabolites in tumor tissue (Zhou et al., 2020). Taken together, the evidence indicates that evidence of OSCC metabolic biomarkers can be extrapolated beyond “case control discrimination to staging aggressiveness stratification in spite of more stringent cohort matching coupled with confounding controls, cross-platform reproducibility, more rigorous targeted quantification workflows and multicenter prospective validation models.