HMGA2 identified via m6A-senescence multi-omics in laryngeal squamous cell carcinoma

N6-methyladenosine (m6A) modification and cellular senescence have been individually implicated in tumor biology, but the landscape of m6A-related senescence genes in laryngeal squamous cell carcinoma (LSCC) remains underexplored. In this study, we conducted an integrated multi-omics analysis combining bulk and single-cell transcriptomics, somatic mutation and copy number variation data, and proteomics to explore the clinical and molecular impacts of m6A-related senescence. We identified 93 putative m6A-related senescence genes with prognostic value, defining molecular subtypes with distinct immune features, survival outcomes, and pathway activities. Further stratification using differentially expressed genes revealed additional heterogeneity, and a derived m6A-related senescence score (m6ASenScore) showed robust associations with prognosis and mutation burden. Single-cell analysis uncovered malignant epithelial subpopulations with subtype-specific metabolic and inflammatory profiles. Among five core candidate genes, HMGA2 was found to be significantly upregulated at the protein level. Functional experiments in LSCC cell lines showed that reducing HMGA2 levels inhibited cell growth, invasion, and migration. This study provides a comprehensive characterization of m6A-related senescence signatures and highlights HMGA2 as a potential therapeutic target in LSCC.