Distinct Plasma Lipid Signatures of Oral Cavity Squamous Cell Carcinoma

Introduction: Oral cavity squamous cell carcinoma (OCSCC) is an aggressive cancer with poor outcomes, primarily due to late-stage diagnoses and frequent recurrence. Current diagnostic methods lack reliable tools for detection. In other types of cancers, tumor-specific lipid profiles have been identified and may also serve as a novel non-invasive biomarker for OCSCC. This study aims to characterize plasma lipid profiles from patients with OCSCC.

Methods: Banked plasma samples from 20 OCSCC patients (T1-T4) and 11 non-cancer controls were analyzed using liquid chromatography mass spectrometry. Four separate lipid profiles were measured: ceramide/sphingosine (Cer-Sph), hexosyl-ceramide (Hex-Cer), lactosyl-ceramide (Lac-Cer), and free fatty acids/prostaglandins (FFA/PG). Group comparisons were performed using students t-test and principal component analysis (PCA).

Results: We found 27 of 64 specific lipids to have significantly different abundance between OCSCC and control. Interestingly, Cer-Sph were found to be lower while FFA/PG were higher in OCSCC compared to control. Differential abundance was not observed amongst Hex-Cer or Lac-Cer species. PCA demonstrated significantly different lipid signatures (p=0.004) between OCSCC and control. Group comparisons by OCSCC stage did not show significant differences. Recurrence was most highly associated with elevated levels of C22-Cer (p=0.002), C24-Cer (p=0.002), C24:1-Cer (p=0.003), and C14-Cer (p=0.003). Additionally, higher levels of C24:1Hex-Cer (p=0.001), C16Hex-Cer (p=0.020), and C16:1-FFA (p=0.029) were linked to increased nodal stage.

Conclusions: Plasma lipid signatures distinguishes patients with OCSCC from non-cancer controls and identifies specific lipid species associated with recurrence and nodal disease. These findings support lipidomics as a promising non-invasive biomarker strategy in OCSCC. Future studies incorporating larger, longitudinal cohorts and paired perioperative samples will be necessary to validate these associations and define their clinical utility.