Appraising histone H4 lysine 5 lactylation as a novel biomarker in breast cancer.

Background Posttranslational modifications of histone lysine (K) have integral connections with cell metabolism, and participate in the carcinogenesis of various cancers. This study focuses on evaluating the expression of histone H4 lys 5 lactylation (H4K5lac) and its clinical role in breast cancer (BC). Methods During this research, immunohistochemistry (IHC) and immunoblotting, utilizing a specific primary anti-L-lactyl-histone H4 (Lys 5) rabbit monoclonal antibody, were employed to assess H4K5lac expression in BC tissue chips. H4K5lac expression in the peripheral blood mononuclear cells (PBMCs) of BC patients was investigated through immunoblotting. Results IHC revealed upregulation of histone H4K5lac in both triple-negative breast cancer (TNBC) and non-TNBC tissues, with positive rate of 91.40% [170/(150 + 19 + 17)] and 93.64% (103/110) in TNBC and non-TNBC tissues, respectively. The expression of H4K5lac demonstrated positive correlations with lymph nodes (%), and Ki-67 expression. Survival analysis indicated a negative correlation between H4K5lac expression and overall survival (OS) time in both TNBC (HR [hazard ratio] = 2.773, 95%CI [confidence interval]: 1.128-6.851, P = 0.0384) and non-TNBC cases (HR = 2.156, 95%CI: 1.011-4.599, P = 0.0275). Furthermore, elevated levels of H4K5lac were observed in the PBMCs of BC cases, and H4K5lac expression is positively correlated with serum lactate and carcinoma embryonic antigen (CEA) levels. Conclusions Histone H4K5lac exhibits increased levels in both BC tissues and PBMCs, suggesting its potential as a promising biomarker for BC. This study might pave the way toward novel lactylation treatment strategies in BC.