Single-Cell RNA Sequencing Reveals Lactylation Modifications in Neuroblastoma and the Construction of a Prognostic Model

Lactylation, a recently identified post-translational modification, has been associated with multiple cancer types, including neuroblastoma (NB). The present study aimed to investigate the prognostic significance of lactylation-related genes and to develop a prognostic model to enhance patient risk stratification and guide targeted therapy for NB. In the present bioinformatics study, single-cell RNA sequencing data (GSE137804) were analyzed to quantify lactylation activity in NB cells using the AddModuleScore algorithm based on 371 lactylation-related genes. A total of 142 differentially expressed lactylation-related genes (DELGs) were identified between high- and low-lactylation tumor cells, and these genes were mainly enriched in cell cycle-related pathways. A 14-gene lactylation-related prognostic model was then constructed using the identified DELGs in a training cohort (GSE49710, n = 349) via Cox and LASSO regression, and validated in internal (GSE49710, n = 149) and external (E-MTAB-8248, n = 223) cohorts. The model effectively stratified patients into high- and low-risk groups with significantly different overall survival (OS) outcomes, and its robust predictive performance was confirmed across both validation cohorts. The present study reveals the significant prognostic role of lactylation in NB, and the 14-gene model serves as a novel molecular tool for risk stratification and provides a reference for developing targeted therapeutic strategies for NB.