The Potential of Lipid Droplet-associated Genes as Diagnostic and Prognostic Biomarkers in Head and Neck Squamous Cell Carcinoma

Objective: The role of lipid droplets (LDs) and lipid droplet-associated genes (LD-AGs) remains unclear in head and neck squamous cell carcinoma (HNSCC). This study aimed to investigate LDs in HNSCC and identify LD-AGs essential for the diagnosis and prognosis of HNSCC patients. Methods: The LDs in the HNSCC and normal cell lines were stained with oil red O. Bioinformatic analysis was used to find LD-AGs in HNSCC that had diagnostic and prognostic significance. Results: LDs accumulation was increased in HNSCC cell lines compared with normal cell lines (P<0.05). Fifty-three differentially expressed genes, including 34 upregulated and 19 downregulated, were found in HNSCC based on the TCGA platform (P<0.05). Then, 53 genes were proved to be functionally enriched in lipid metabolism and LDs. Among them, with an AUC value > 0.7, 34 genes demonstrated a high predictive power. Six genes (AUP1, CAV1, CAV2, CAVIN1, HILPDA, and SQLE) out of 34 diagnostic genes were linked to overall survival in patients with HNSCC (P<0.05). The significant prognostic factors AUP1, CAV1, CAV2, and SQLE were further identified using the univariate and multivariate cox proportional hazard models (P<0.05). The protein expression of CAV2 and SQLE was significantly increased in the HNSCC tissue compared to normal tissues (P<0.05). Finally, the knockdown of the four LD-AGs decreased LDs accumulation, respectively. Conclusions: Increased LDs accumulation was a hallmark of HNSCC, and AUP1, CAV1, CAV2, and SQLE were discovered as differentially expressed LD-AGs with diagnostic and prognostic potential in HNSCC.