Abstract
INTRODUCTION AND AIMS: Oral squamous cell carcinoma (OSCC) represent a frequently occurring malignant neoplasm in the head and neck region, characterized by a high rate and poor prognosis. Current research on lipid metabolism predominantly centers on inducing lipotoxicity through the disruption of lipid homeostasis and the reduction of signaling lipid availability, which has been demonstrated to inhibit the progression of OSCC. METHODS: To figure out the risk with weak prognosis, we conducted a dual validation with a multi-omics approach combining Mendelian randomization (MR) and single-cell RNA sequencing(scRNA-seq). RESULTS: This strategy enabled us to conclude that the Lipid_Low cell population, a subpopulation of malignant cells with low correlation with glycerophospholipid (GP) metabolism, was associated with poor prognostic properties of OSCC patients. This characteristic was accompanied by stronger migratory ability, proliferative activity, and possible immune escape characteristics. The Lipid_Low subpopulation may represent a class of clinically significant high-risk cellular states. CONCLUSION: In terms of transcriptional features, Lipid-associated Low-malignancy cells may be significantly correlated with poor patient prognosis, thereby providing a foundation for future research into targeted therapeutic strategies. CLINICAL RELEVANCE: These findings also suggest that lipid metabolism could serve as a potential biomarker for assessing the clinical prognosis of patients with OSCC.