Identification of GADD45B, HMGB3, LMNB2, and MFAP5 as lactylation-related prognostic markers for survival prediction in esophageal cancer

Background: Lactylation, a protein modification driven by lactate produced during glycolysis, has been implicated in tumorigenesis and immune suppression, and may influence patient prognosis. This study aimed to identify lactylation-related prognostic genes and explore their potential functional relevance. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to identify lactylation-related genes (LRGs) in esophageal cancer (ESCA). Prognostic LRGs were determined by univariate and multivariate Cox regression analyses. Correlations of prognostic LRGs with ESCA-associated genes, immune cell infiltration, and five classes of immunomodulatory genes were evaluated, followed by functional enrichment and drug sensitivity analyses. These LRGs were validated using an independent dataset and immunohistochemistry (IHC) assays. Results: A total of 321 predictive LRGs were identified in ESCA. Four LRGs (GADD45B, HMGB3, LMNB2, and MFAP5) were further recognized as independent prognostic factors (P