Systemic Inflammation, Tumor Isotopic Signatures, and Prognosis in Oral Squamous Cell Carcinoma: Exploratory...

Background/Objectives: Oral squamous cell carcinoma (OSCC) remains clinically heterogeneous, and prognosis is not always fully explained by conventional clinicopathological parameters. Systemic inflammation and tumor metabolic alterations may provide complementary information on tumor biology. This study aimed to assess associations between preoperative inflammatory markers, isotope ratio mass spectrometry (IRMS)-derived tumor signatures, clinicopathological features, and survival outcomes in OSCC. Methods: This exploratory retrospective secondary analysis included 50 consecutive patients with surgically treated, histologically confirmed OSCC. Preoperative blood-based markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), white blood cell count, lymphocyte count, and C-reactive protein, were retrieved from routine laboratory tests. Matched tumor, surgical margin, and healthy oral mucosa samples were analyzed by IRMS for δ¹³C, δ¹⁵N, carbon and nitrogen content, and [N]/[C] ratio. Associations with clinicopathological variables, nodal status, overall survival (OS), and disease-free survival (DFS) were evaluated using non-parametric tests, Spearman correlations, and Cox regression models. Results: Tumor tissue showed a consistent isotope and elemental phenotype compared with healthy mucosa, including higher nitrogen content, lower carbon content, increased [N]/[C] ratio, lower δ¹⁵N, and less negative δ¹³C values. NLR, PLR, SII, and CRP were not robustly associated with standard clinicopathological features after correction for multiple testing. Correlations between inflammatory and isotope-derived parameters were modest. Higher NLR was associated with worse OS and DFS and remained significant after adjustment for pathologic nodal status. Less negative tumor δ¹³C showed a potential adverse prognostic signal. Conclusions: Systemic inflammatory markers and IRMS-derived tumor signatures appear to reflect partly distinct biological domains in OSCC. NLR may provide accessible prognostic information, while tumor δ¹³C warrants further validation as a metabolic biomarker.