Abstract / Summary
Abstract Background: Oral squamous cell carcinoma (OSCC) involves complex interactions between tumor-associated inflammation and immune regulatory pathways. This study aimed to characterize circulating inflammatory cytokines and tumor necrosis factor (TNF) superfamily members and their contribution to systemic immune dysregulation in OSCC.
Methods: Serum samples from OSCC patients and healthy controls were analyzed using multiplex immunoassays. Inflammatory cytokines and TNF superfamily markers were compared between groups. Associations were assessed by Spearman correlation analysis. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curves, and multivariable logistic regression assessed associations with nodal metastasis and UICC stage.
Results: IL-6 and MCP-1 were significantly elevated in OSCC patients, while OPG, TWEAK, and LIGHT were increased among TNF superfamily members. IL-6 correlated with IL-8, IL-17A, TNF-α, IL-1β, and IP-10, indicating a coordinated inflammatory network. OPG, TWEAK, and LIGHT also showed structured intercorrelations, while IL-6 and MCP-1 were associated with OPG and TWEAK, suggesting cross-talk between inflammatory and TNF-related pathways. ROC analysis showed modest diagnostic performance for IL-6 (AUC 0.631) and MCP-1 (AUC 0.618), whereas OPG reached an AUC of 0.749. A combined IL-6/OPG/LIGHT score showed the best performance (AUC 0.788). Log10-transformed IL-6 was independently associated with nodal metastasis and advanced UICC stage.
Conclusions: OSCC is associated with coordinated systemic alterations in inflammatory and TNF-related signaling. Integrated biomarker approaches may improve diagnostic performance and provide greater translational relevance than single markers. Clinical Relevance: Circulating immune signatures combining inflammatory and TNF-related markers may complement established clinical parameters in OSCC. Especially, multimarker signatures warrant further validation as non-invasive tools for patient stratification.