Abstract
BACKGROUND: Lactylation has been implicated in tumor growth, proliferation, and metastasis; however, its precise relationship with cancer remains poorly understood. This study aims to elucidate the role of lactylation-related genes (LRGs) in the development of endometrial cancer (EC). METHODS: We utilized data from The Cancer Genome Atlas (TCGA) database to analyze the expression and mutation patterns of LRGs in EC. Univariate Cox regression analysis and Lasso-Cox regression analysis were employed to identify prognosis-related genes and construct a risk model. EC samples were stratified into high-risk and low-risk groups based on the risk values derived from the model. These groups were validated using both training and validation cohorts. Additionally, we assessed differences in the immune microenvironment, tumor mutation burden (TMB), and drug response between the high-risk and low-risk groups. RESULTS: Differentially expressed genes (DEGs) between EC and control samples were identified, and their intersection with LRGs yielded differentially expressed lactylation-related genes (DLRGs). A total of six prognostic DLRGs (PFKM, H3C1, SIRT3, VIM, WAS, and LSP1) were selected and used to construct an EC risk model. Significant differences in prognosis, immune microenvironment, TMB, and drug sensitivity were observed between the high-expression and low-expression groups. CONCLUSION: LRGs play a significant role in endometrial cancer by influencing cell growth, the immune microenvironment, and drug response. The six DLRGs included in the risk model may serve as potential prognostic markers and therapeutic targets for EC.