Lactylation Signatures as Predictors of Prognosis and Therapeutic Response in Lung Adenocarcinoma: Implications for Ultrasound-Based Therapeutic Strategies

Background: Lactylation, a unique post-translational alteration, has been identified as an important epigenetic regulator of cancer metabolism, immune evasion, and treatment resistance. Recent research reveals that ultrasound-based biophysical stimulation may change tumor microenvironmental variables that affect lactate metabolism and subsequent lactylation processes. The purpose of this study was to better understand the predictive significance of lactylation-associated genes in lung adenocarcinoma (LUAD) and how they could interact with ultrasound-mediated treatment response. Methods: Transcriptomic data from 867 LUAD samples were used to identify lactylation-related genes. Consensus clustering was used to separate LUAD cases into various lactylation subtypes. Differentially expressed genes were assessed for functional enrichment, mutation load, and immunological infiltration. A prognostic risk model was created using multivariate Cox regression analysis. Results: Nineteen major lactylation-related genes divided patients with LUAD into three molecular subgroups with different clinical outcomes. A 10-gene prognostic model accurately predicted overall survival and was associated with stronger tumor stemness, increased mutational frequency, and decreased immunotherapy effectiveness in high-risk patients. Notably, computational predictions suggested that metabolic regulation might slow lactylation-driven tumor development, implying a synergistic treatment window. Conclusion: Lactylation-associated gene profiles may serve as prognostic biomarkers and therapeutic modulators in LUAD. The combination of ultrasound-based therapies targeting lactylation pathways could be a viable technique for improving precision oncology and overcoming resistance mechanisms in lung cancer therapy.