Lactylproteome analysis indicates histone H4K12 lactylation as a novel biomarker in triple-negative breast cancer
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View abstract on PubMed
Summary
This summary is machine-generated.Triple-negative breast cancer (TNBC) shows altered lactylation patterns. Histone H4K12 lactylation (H4K12lac) is upregulated in TNBC and may serve as a prognostic biomarker for improved patient outcomes.
Area Of Science
- Biochemistry
- Molecular Biology
- Oncology
Background
- Posttranslational modifications of lysine residues, including lactylation, are increasingly recognized for their roles in cell metabolism and cancer progression.
- While the link between lysine modifications and cancer is established, the specific lactylation signature in triple-negative breast cancer (TNBC) remains largely unexplored.
Purpose Of The Study
- To comprehensively profile lactylation in TNBC and identify potential biomarkers.
- To investigate the clinicopathological and prognostic significance of identified lactylated proteins, particularly histone modifications.
Main Methods
- Utilized 4-Dimensional label-free quantitative proteomics combined with lactylation analysis (4D-LFQP-LA) on TNBC and adjacent tissue samples.
- Employed immunoblotting and immunohistochemistry (IHC) to validate the expression of identified lactylated proteins.
- Performed bioinformatic and functional analyses to understand the roles of lactylated proteins.
Main Results
- Identified 58 lactylation sites on 48 proteins, revealing a distinct lactylation alteration signature in TNBC.
- Found significant upregulation of lactylation at lysine 12 of histone H4 (H4K12lac) in TNBC tissues (prevalence >92% in cohorts).
- H4K12lac expression positively correlated with Ki-67 and inversely with overall survival, indicating its potential as an independent prognostic marker (HR=3.477, P=0.011).
Conclusions
- Lactylation represents a significant posttranslational modification in TNBC.
- H4K12lac is a promising biomarker for TNBC, offering insights into lactylation profiles and linking histone modifications to clinical outcomes.
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