{"title":"新型生物标志物对乳腺癌治疗相关心功能障碍的早期诊断价值","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":"{\"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}","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
摘要
目的：本研究旨在(1)通过meta分析评估髓过氧化物酶（MPO）、生长分化因子-15 （GDF-15）、c反应蛋白（CRP）、胎盘生长因子（PLGF）和半乳糖凝集素-3 （Gal-3）对乳腺癌患者癌症治疗相关性心功能障碍（CTRCD）的诊断价值；(2)使用孟德尔随机化（MR）研究因果关系。方法：采用双相分析。首先，对来自5个数据库（PubMed/Web of Science/Embase/Cochrane/ClinicalTrials.gov）的12项研究（11个前瞻性队列，1个随机对照试验，917例患者，年龄50.4±16.0岁，中位随访12个月）进行meta分析，通过加权/标准化平均差异（WMD/SMD）和通过风险比（hr）量化治疗后生物标志物的变化。其次，双样本MR分析利用mpo相关的单核苷酸多态性（snp）来评估与心力衰竭（HF）和心肌病的因果关系，采用IVW、MR- egger、加权中位数和简单模式方法进行异质性检验。结果：荟萃分析显示治疗后MPO显著升高[美国患者：SMD = 0.78, 95%可信区间（CI） 0.45-1.12；i2 = 72%；p 2 = 77%；P = 0.002), PLGF (SMD = 0.87, 95% CI 0.10 - -1.63; I2 = 95%; P = 0.03),和c反应蛋白(大规模杀伤性武器= 0.83,95% CI 0.46 - -1.20; I2 = 18%; P 2 = 0%)和PLGF (I2 = 0%),而部分降低MPO的异质性(I2 = 72%)。MPO水平升高预示接受癌症治疗的患者CTRCD风险增加（HR = 1.30, 1.10-1.54; I2 = 0%; P = 0.002）。MR分析显示MPO与两种HF之间存在因果关系[比值比(OR) = 1.06, 95% CI 1.02-1.09；P = 0.001]和心肌病（OR = 1.09, 95% CI 1.02-1.17; P = 0.02），心衰snp存在显著异质性（科克伦Q = 61.63, P = 0.04）。结论：我们的研究表明MPO与CTRCD发病机制的诊断生物标志物和机制途径都有关。这些初步发现突出了MPO作为进一步研究乳腺癌患者早期CTRCD检测的可能靶点。
Early diagnostic value of novel biomarkers for breast cancer therapy-related cardiac dysfunction.
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.
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