Single-cell multi-omics reveals NUF2 as a potential biomarker associated with the high-lactylation malignant state in osteosarcoma.

BackgroundLactylation has emerged as a crucial post-translational modification that influences oncogenesis and tumor progression. However, its intratumoral heterogeneity in osteosarcoma is not well characterized.MethodsSingle-cell multi-omics data were retrieved from the Gene Expression Omnibus database. Lactylation heterogeneity was assessed, cell-cell communication networks were constructed, and transcription factor activity was analyzed to delineate differences among cell populations. Bioinformatics analysis coupled with experimental validation was employed to screen for potential targets.ResultsThe study revealed that the overall lactylation level was significantly elevated in osteosarcoma tissues compared to adjacent non-tumor tissues. At the single-cell level, osteosarcoma-derived osteoblastic cells exhibited markedly higher lactylation scores than their counterparts from adjacent non-tumor tissue. Bioinformatics analysis identified NUF2 as a potential biomarker associated with the high-lactylation malignant state. Subsequent experimental validation confirmed that NUF2 is overexpressed in osteosarcoma tissues and co-localizes with pan-Kla.ConclusionThis study presents a single-cell lactylation atlas of osteosarcoma, identifies NUF2 as a potential biomarker associated with the high-lactylation malignant state, and provides a novel theoretical basis for the clinical translation of lactylation-targeted therapies.