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ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Cancer Endocrinology
Volume 15 - 2024 |
doi: 10.3389/fendo.2024.1328679
Lactylproteome analysis indicates histone H4K12 lactylation as a novel biomarker in triple-negative breast cancer
Provisionally accepted
Zhaolei Cui
1
Yanhong Li
2*
Yingying Lin
2
Chaoqiang Zheng
2*
Lingqing Luo
2*
Dan Hu
2
Yan Chen
2
Zhenzhou Xiao
2*
Sun Yang
2*- 1 Fujian Medical University, Fuzhou, China
- 2 Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, China
Objective: The established link between posttranslational modifications of histone and non-histone lysine (K) residues in cell metabolism, and their role in cancer progression, is well-documented. However, the lactylation expression signature in triple-negative breast cancer (TNBC) remains underexplored. Methods: We conducted a comprehensive lactylproteome profiling of eight pairs of TNBC samples and their matched adjacent tissues. This was achieved through 4-Dimensional label-free quantitative proteomics combined with lactylation analysis (4D-LFQP-LA). The expression of identified lactylated proteins in TNBC was detected using immunoblotting and immunohistochemistry (IHC) with specific primary antibodies, and their clinicopathological and prognostic significance was evaluated. Results: Our analysis identified 58 lactylation sites on 48 proteins, delineating the protein lactylation alteration signature in TNBC. Bioinformatic and functional analyses indicated that these lactylated proteins play crucial roles in regulating key biological processes in TNBC. Notably, lactylation of lysine at position 12 (H4K12lac) in the histone H4 domain was found to be upregulated in TNBC. Further investigations showed a high prevalence of H4K12lac upregulation in TNBC, with positive rates of 93.19% (137/147) and 92.29% (92/99) in TNBC tissue chip and validation cohorts, respectively. H4K12lac expression correlated positively with Ki-67 and inversely with overall survival (OS) in TNBC (HR [hazard ration] =2.813, 95%CI [credibility interval]: 1.242-6.371, P=0.0164), suggesting its potential as an independent prognostic marker (HR=3.477, 95%CI: 1.324-9.130, P=0.011). Conclusions: Lactylation is a significant post-translational modification in TNBC proteins. H4K12lac emerges as a promising biomarker for TNBC, offering insights into the lactylation profiles of TNBC proteins and linking histone modifications to clinical implications in TNBC.
Keywords: Triple negative breast cancer, Histone H4, lactylation, biomarker, prognosis
Received: 27 Oct 2023; Accepted: 28 Mar 2024.
Copyright: © 2024 Cui, Li, Lin, Zheng, Luo, Hu, Chen, Xiao and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yanhong Li, Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, China
Chaoqiang Zheng, Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, China
Lingqing Luo, Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, China
Zhenzhou Xiao, Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, China
Sun Yang, Fujian Provincial Cancer Hospital, Fuzhou, Fujian Province, China
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