Comprehensive Analysis of Lactylation-Related Genes in Peripheral T-Cell Lymphoma

Background Lactylation is an emerging post-translational modification that plays an important role in tumour progression. Peripheral T-cell lymphoma (PTCL) is a rare but highly heterogeneous subtype of non-Hodgkin lymphomas with limited effective therapeutic options. This study aimed to investigate the potential prognostic role of lactylation-related genes (LRGs) in PTCL. Methods Gene expression profiles and corresponding clinical data of patients with PTCL were obtained from the Gene Expression Omnibus database. LRGs were identified by integrating differentially expressed genes and genes positively correlated with the lactylation score. Key modules associated with the lactylation score were identified using weighted gene co-expression network analysis. Univariate Cox regression and random survival forest analyses were subsequently used to construct a prognostic model, which was further validated using the GSE90597 dataset. Functional enrichment, immune microenvironment, drug sensitivity, and model gene expression analyses were performed. Results Five key LRGs were identified and used to construct a lactylation-related prognostic model which was further evaluated in the GSE90597 dataset as exploratory external validation. The model effectively stratified patients with PTCL into high- and low-risk groups with distinct pathway enrichment, immune infiltration, and predicted drug sensitivity profiles. Notably, the high-risk group was significantly enriched in proliferation-related pathways and exhibited an immune-cold microenvironmental phenotype. In addition, the differential expression of the model genes between reactive lymph nodes and PTCL tumour tissues was validated using the GSE115917 and GSE263321 datasets. Conclusion The lactylation-related prognostic model may serve as a potential tool for prognostic assessment and individualised treatment stratification of PTCL, suggesting that lactylation-related molecular features may be involved in PTCL progression.