Background Triple-negative breast cancer (TNBC) is an aggressive subtype of breast malignancy characterized by poor clinical outcomes and limited therapeutic options. The identification of reliable biomarkers for predicting prognosis and immunotherapeutic response remains an urgent clinical need. This study aimed to develop an integrative lactylation-related gene signature to simultaneously evaluate prognostic trajectories and immunotherapeutic sensitivity in TNBC. Methods Transcriptomic and clinical data from public TNBC cohorts were systematically analyzed. Lactylation-related gene signatures were used to stratify patients via consensus clustering. A scoring model was constructed based on differentially expressed genes between clusters, and its associations with immune infiltration, pathway enrichment, drug sensitivity, and clinical outcomes were evaluated. Finally, quantitative real-time polymerase chain reaction, Western blot and Confocal immunofluorescence Microscopy were used to validate the hub genes. Results Significant gene expression differences stratified TNBC patients into high- and low-score groups, with the high-score group demonstrating superior clinical outcomes. These patients also showed better responses to immunotherapy, as indicated by immune checkpoint profiles and chemotherapy sensitivity. Experimental validation confirmed Programmed Cell Death 1 Ligand 2, Immunoglobulin J Chain, and Colony Stimulating Factor 2 Receptor Beta as key molecular nodes. Our scoring model predicts immunotherapy efficacy, and these three genes may represent potential candidates for further therapeutic exploration in TNBC. Conclusions This study establishes a novel lactylation-related gene signature that effectively predicts both prognosis and immunotherapeutic sensitivity in TNBC. The identified hub genes represent promising biomarkers and potential therapeutic targets warranting further investigation.
Wang et al. (2026) studied this question.