{"title":"Early diagnostic value of novel biomarkers for breast cancer therapy-related cardiac dysfunction.","authors":"Zhengwei Wang, Yujuan Wu, Jingyi He, Diansa Gao, Zhong Zuo","doi":"10.1002/ehf2.15363","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>This study aims to (1) evaluate the diagnostic utility of myeloperoxidase (MPO), growth differentiation factor-15 (GDF-15), C-reactive protein (CRP), placental growth factor (PLGF) and galectin-3 (Gal-3) for cancer therapy-related cardiac dysfunction (CTRCD) in breast cancer patients through meta-analysis and (2) investigate causal roles using Mendelian randomization (MR).</p><p><strong>Methods: </strong>We conducted a dual-phase analysis. First, a PRISMA-compliant (ID: CRD42023453369) meta-analysis of 12 studies (11 prospective cohorts, 1 RCT; 917 patients; age 50.4 ± 16.0 years; median follow-up 12 months) from five databases (PubMed/Web of Science/Embase/Cochrane/ClinicalTrials.gov) quantified post-treatment biomarker changes using weighted/standardized mean differences (WMD/SMD) and CTRCD risk via hazard ratios (HRs). Second, two-sample MR analysis leveraged MPO-associated single nucleotide polymorphisms (SNPs) to assess causality with heart failure (HF) and cardiomyopathy, employing IVW, MR-Egger, weighted median and simple mode methods with heterogeneity testing.</p><p><strong>Results: </strong>The meta-analysis demonstrated significant post-treatment elevations in: MPO [US patients: SMD = 0.78, 95% confidence interval (CI) 0.45-1.12; I<sup>2</sup> = 72%; P < 0.00001], GDF-15 (SMD = 0.64, 95% CI 0.24-1.05; I<sup>2</sup> = 77%; P = 0.002), PLGF (SMD = 0.87, 95% CI 0.10-1.63; I<sup>2</sup> = 95%; P = 0.03), and CRP (WMD = 0.83, 95% CI 0.46-1.20; I<sup>2</sup> = 18%; P < 0.0001). Subgroup analyses eliminated heterogeneity for GDF-15 (I<sup>2</sup> = 0%) and PLGF (I<sup>2</sup> = 0%), while partially reducing heterogeneity for MPO (I<sup>2</sup> = 72%). Elevated MPO levels predicted increased CTRCD risk in patients receiving cancer treatment (HR = 1.30, 1.10-1.54; I<sup>2</sup> = 0%; P = 0.002). MR analysis suggested causal relationships between MPO and both HF [odds ratio (OR) = 1.06, 95% CI 1.02-1.09; P = 0.001] and cardiomyopathy (OR = 1.09, 95% CI 1.02-1.17; P = 0.02), with significant heterogeneity detected in heart failure SNPs (Cochran's Q = 61.63, P = 0.04).</p><p><strong>Conclusions: </strong>Our study suggested that MPO was associated with both diagnostic biomarker profiles and mechanistic pathways in CTRCD pathogenesis. These preliminary findings highlighted MPO as a possible target for further investigation of early CTRCD detection in breast cancer patients.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ESC Heart Failure","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/ehf2.15363","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
Aims: This study aims to (1) evaluate the diagnostic utility of myeloperoxidase (MPO), growth differentiation factor-15 (GDF-15), C-reactive protein (CRP), placental growth factor (PLGF) and galectin-3 (Gal-3) for cancer therapy-related cardiac dysfunction (CTRCD) in breast cancer patients through meta-analysis and (2) investigate causal roles using Mendelian randomization (MR).
Methods: We conducted a dual-phase analysis. First, a PRISMA-compliant (ID: CRD42023453369) meta-analysis of 12 studies (11 prospective cohorts, 1 RCT; 917 patients; age 50.4 ± 16.0 years; median follow-up 12 months) from five databases (PubMed/Web of Science/Embase/Cochrane/ClinicalTrials.gov) quantified post-treatment biomarker changes using weighted/standardized mean differences (WMD/SMD) and CTRCD risk via hazard ratios (HRs). Second, two-sample MR analysis leveraged MPO-associated single nucleotide polymorphisms (SNPs) to assess causality with heart failure (HF) and cardiomyopathy, employing IVW, MR-Egger, weighted median and simple mode methods with heterogeneity testing.
Results: The meta-analysis demonstrated significant post-treatment elevations in: MPO [US patients: SMD = 0.78, 95% confidence interval (CI) 0.45-1.12; I2 = 72%; P < 0.00001], GDF-15 (SMD = 0.64, 95% CI 0.24-1.05; I2 = 77%; P = 0.002), PLGF (SMD = 0.87, 95% CI 0.10-1.63; I2 = 95%; P = 0.03), and CRP (WMD = 0.83, 95% CI 0.46-1.20; I2 = 18%; P < 0.0001). Subgroup analyses eliminated heterogeneity for GDF-15 (I2 = 0%) and PLGF (I2 = 0%), while partially reducing heterogeneity for MPO (I2 = 72%). Elevated MPO levels predicted increased CTRCD risk in patients receiving cancer treatment (HR = 1.30, 1.10-1.54; I2 = 0%; P = 0.002). MR analysis suggested causal relationships between MPO and both HF [odds ratio (OR) = 1.06, 95% CI 1.02-1.09; P = 0.001] and cardiomyopathy (OR = 1.09, 95% CI 1.02-1.17; P = 0.02), with significant heterogeneity detected in heart failure SNPs (Cochran's Q = 61.63, P = 0.04).
Conclusions: Our study suggested that MPO was associated with both diagnostic biomarker profiles and mechanistic pathways in CTRCD pathogenesis. These preliminary findings highlighted MPO as a possible target for further investigation of early CTRCD detection in breast cancer patients.
期刊介绍:
ESC Heart Failure is the open access journal of the Heart Failure Association of the European Society of Cardiology dedicated to the advancement of knowledge in the field of heart failure. The journal aims to improve the understanding, prevention, investigation and treatment of heart failure. Molecular and cellular biology, pathology, physiology, electrophysiology, pharmacology, as well as the clinical, social and population sciences all form part of the discipline that is heart failure. Accordingly, submission of manuscripts on basic, translational, clinical and population sciences is invited. Original contributions on nursing, care of the elderly, primary care, health economics and other specialist fields related to heart failure are also welcome, as are case reports that highlight interesting aspects of heart failure care and treatment.