Lactylation Plays a Novel Role in the Tumor Microenvironment and its Prognostic Implications for Breast Cancer.

[INTRODUCTION] This study aims to develop a predictive signature based on lactylation to complement existing staging systems and improve prognostic accuracy in clinical settings.

[METHODS] A database of lactylation-associated genes was obtained from The Cancer Genome Atlas (TCGA). Cox and LASSO regression analyses were used to identify a risk signature. Differential expression and enrichment analyses were performed to explore functional differences between these groups, and the influence of lactylation-associated genes on the tumor immune microenvironment and chemotherapy sensitivity was evaluated. After screening for lactylationassociated genes highly expressed and prognostically relevant in BC, in vitro assays were conducted to examine the role of these genes in tumor proliferation and metastasis.

[RESULTS] We identified six lactylation-associated genes, including SH3GL1, XRCC4, PCMT1, DECR1, ALDH1A1, and RPL14. XRCC4 was highly expressed and identified as a significant factor affecting patients' overall survival in BC. Patients in the high-risk groups exhibited poorer prognoses compared to those in the low-risk groups. Tumor mutation burden, chemotherapeutic sensitivity, and immune infiltration differed significantly between the two groups.

[DISCUSSION] Our results propose XRCC4 as a potential therapeutic target in BC. Although the current evidence is constrained, we are actively expanding the sample size and will develop dedicated validation cohorts to corroborate the lactylation-related findings.

[CONCLUSION] Our findings highlight the potential of lactylation-associated genes, particularly XRCC4, in BC progression and clinical treatment strategies. The development of an XRCC4 inhibitor may be eligible for patent protection and could potentially serve as a novel therapeutic option for BC.