Integrative Analysis of 4-Hydroxynonenal-Modified Proteins and Plasma Metabolome in Breast Cancer Patients

Jaganjac, Morana; Nikolac Perković, Matea; Horvat, Tea; Rojo, David; Krizic, Marija; Dedic Plavetic, Natalija; Vrbanec, Damir; Orehovec, Biserka; Zarkovic, Kamelija; Žarković, Neven (2026) Integrative Analysis of 4-Hydroxynonenal-Modified Proteins and Plasma Metabolome in Breast Cancer Patients. Antioxidants, 15 (2). ISSN 2076-3921

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Abstract

Breast cancer is a highly heterogeneous malignancy, characterized by diverse genetic, epigenetic, and phenotypic variations, as well as by metabolic reprogramming and oxidative stress. Lipid peroxidation bioactive product 4-hydroxynonenal (4-HNE) plays a significant role in the development and progression of cancer. In this study, we quantified circulating 4-HNE-modified proteins and performed comprehensive untargeted metabolomic profiling of the patients’ plasma using LC-ESI-QTOF-MS and GC-EI-QMS, aiming to investigate systemic metabolic pathways associated with oxidative damage in breast cancer. Significantly elevated levels of 4-HNE-modified proteins were detected in breast cancer patients compared to healthy controls, accompanied by distinct metabolomic signatures enriched in lipid metabolism. Several metabolites, including specific long-chain fatty acids, exhibited significant correlations with circulating 4-HNE-modified proteins, suggesting an interaction between lipid peroxidation-driven protein modification and breast cancer-associated metabolic reprogramming. Overall, this study provides evidence of associations between systemic 4-HNE-mediated protein modification and altered metabolic profiles in breast cancer, highlighting oxidative stress–related metabolites as potential biomarkers and pointing to redox-metabolic crosstalk in breast cancer patients.

Item Type:	Article
Uncontrolled Keywords:	breast cancer; lipid peroxidation; 4-hydroynonenal; metabolome remodeling
Subjects:	BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions:	Division of Molecular Medicine
Depositing User:	Ema Buhin Šaler
Date Deposited:	24 Feb 2026 12:26
URI:	http://fulir.irb.hr/id/eprint/11243
DOI:	10.3390/antiox15020265

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