Increasing CYLD expression improved the prognosis by downregulating the mTOR/SREBP1/lipid metabolism pathway in HPV-negative OSCC patients

Background: CYLD is associated with tumorigenesis, but its role in HPV-negative OSCC is unclear. Methods and Results: R-bioinformatics analysis from the GEO database and qPCR analysis of OSCC cell lines demonstrated that CYLD mRNA expression was significantly reduced in OSCC compared to normal tissue and normal human gingival epithelial cell lines. In 66 primary OSCC cases, immunohistochemistry revealed decreased CYLD expression in OSCC tissues. High expression of CYLD was negatively associated with OSCC recurrence in HPV-negative patients (p=0.04) and correlated with improved overall survival (OS) and disease-free survival (DFS) (p=0.02 and 0.01, respectively). CCK-8, wound healing, and Transwell assays showed that Overexpression of the CYLD group reduced OSCC proliferation, migration, and invasion in UM1 and HN6 cells compared to the Vector group. Lipidomics analysis revealed significantly lower levels of lipid subclasses in the overexpression of the CYLD group. Western blot and qPCR show that overexpression of the CYLD group inhibited mTOR phosphorylation and lipid metabolism in OSCC cells. Conclusion: CYLD expression is significantly reduced in OSCC. Elevating CYLD expression improves OS and DFS by inhibiting the mTOR pathway associated with lipid metabolism in HPV-negative OSCC.