Key result
Elevated serum HMGN2 identifies prevalent HFrEF with good accuracy, yielding an AUC of ~0.81.
Why the study?
Lactate and lactylation are associated with the development of HFrEF, motivating the identification of lactylation-related biomarkers with diagnostic and prognostic value in these patients.
Does serum HMGN2 accurately diagnose prevalent HFrEF and predict poor outcomes in patients with HFrEF?
Observational (n=461)
Does serum HMGN2 accurately diagnose prevalent HFrEF and predict poor outcomes in patients with HFrEF?
Serum HMGN2 is a novel lactylation-associated biomarker that demonstrates good diagnostic discrimination (AUC 0.81) for prevalent HFrEF and is associated with 12-month poor outcomes.
Answers are grounded in this paper and cite their sources.
May support HMGN2 evaluation as HFrEF biomarker; extends lactylation associations but remains hypothesis-generating.
Background/Objectives: Lactate and lactylation are associated with the development of heart failure with reduced ejection fraction (HFrEF). This study aimed to identify potential lactylation-related biomarkers with diagnostic and prognostic value in patients with HFrEF. Methods: We identified the potential lactylation-related biomarkers for heart failure (HF) by integrating bioinformatics analysis with machine learning algorithms. A total of 251 patients with HFrEF and 210 adults without HF were enrolled to validate the diagnostic values of lactylation-related biomarkers at both the mRNA and protein levels. Results: Bioinformatics analysis and machine learning identified EIF4G1, HLTF, HMGN2, LSP1, and PPM1G as hub lactylation-related genes in patients with HF. In the external validation cohort, elevated serum high-mobility group nucleosomal-binding domain 2 (HMGN2) levels were significantly associated with HFrEF. Beyond its diagnostic utility in HFrEF, HMGN2 was associated with prevalent HFrEF (AUC 0.81, 95% CI 0.77–0.85). In exploratory 12-month follow-up, higher HMGN2 was associated with poor outcomes. Conclusions: HMGN2 is a lactylation-associated biomarker that is elevated in patients with HFrEF, associated with prevalent HFrEF, and shows promise for risk stratification with diagnostic discrimination.
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Yu et al. (2026) conducted an observational in Heart failure with reduced ejection fraction (HFrEF) (n=461). Elevated serum HMGN2 levels (lactylation-related biomarker) vs. Adults without heart failure / lower HMGN2 levels was evaluated on Prevalent heart failure with reduced ejection fraction (HFrEF) (AUC 0.81, 95% CI 0.77-0.85). Elevated serum HMGN2 was significantly associated with prevalent HFrEF, demonstrating diagnostic discrimination with an AUC of 0.81 (95% CI 0.77-0.85).
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