Cholesteryl ester and cholesterol as candidate biomarkers for differentiating primary lung squamous cell carcinoma from head and neck squamous cell carcinoma; proof-of-concept biomarker study.

INTRODUCTION

Distinguishing primary lung squamous cell carcinoma (PLSCC) from pulmonary metastases of head and neck squamous cell carcinoma (HNSCC) is clinically critical because treatment strategies differ. However, existing diagnostic approaches, including clinical features, imaging, and immunohistochemistry, remain limited in reliability. Lipidomics offers a potential approach for identifying candidate biomarkers.

METHODS

In this exploratory discovery study, lipid profiles from 10 PLSCC and 20 HNSCC tissue samples were analyzed using liquid chromatography-tandem mass spectrometry to identify candidate lipid biomarkers associated with differences between PLSCC and HNSCC. The lipid profiles of the two groups were compared, and the discriminatory ability of lipid biomarkers exhibiting significant differences in abundance was evaluated using receiver operating characteristic (ROC) and precision-recall analyses.

RESULTS

Among 28 identified lipid classes, cholesteryl ester (ChE) and cholesterol (Ch) were significantly elevated in PLSCC compared with HNSCC (ChE: 2.72-fold, P = 0.012; Ch: 2.19-fold, P = 0.015). Both candidate biomarkers demonstrated potential discriminatory ability, with areas under the ROC curve (ChE: 0.84; Ch: 0.81) and precision-recall curve (ChE: 0.85; Ch: 0.83). In a small exploratory analysis of five lung tumors in patients with prior HNSCC, lipid-based classification was concordant with conventional clinical assessment in some cases and discordant in others.

CONCLUSIONS

ChE and Ch were identified as candidate lipid biomarkers associated with differences between PLSCC and HNSCC. These preliminary findings suggest that lipidomic profiling may provide a complementary approach for distinguishing PLSCC from pulmonary metastases of HNSCC, although independent validation in larger cohorts is warranted.