Lakhani Hari Vishal, Pillai Sneha S, Zehra Mishghan, Dao Benjamin, Tirona Maria Tria, Thompson Ellen, Sodhi Komal
Departments of Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV, 25755, USA.
Division of Cardiology, Department of Internal Medicine, Marshall University Joan C. Edwards School of Medicine, Huntington, WV, 25755, USA.
Sci Rep. 2021 Apr 12;11(1):7954. doi: 10.1038/s41598-021-87209-8.
Cardiotoxic manifestation associated with breast cancer treatment by anthracycline regimen increases patients' susceptibility to myocardial injury, reduction in left ventricular ejection fraction and complications associated with heart failure. There is currently no standardized, minimally invasive, cost effective and clinically verified procedure to monitor cardiotoxicity post-anthracycline therapy initiation, and to detect early onset of irreversible cardiovascular complications. This study aims to create a panel of novel biomarkers and circulating miRNAs associated with cardiotoxicity, further assessing their correlation with cardiac injury specific markers, troponin I and T, and demonstrate the development of cardiac dysfunction in breast cancer patients. Blood obtained from West Virginian females clinically diagnosed with breast cancer and receiving anthracyclines showed upregulated level of biomarkers and circulating miRNAs after 3 and 6 months of chemotherapy initiation with increased levels of cardiac troponin I and T. These biomarkers and miRNAs significantly correlated with elevated troponins. Following 6 months of anthracycline-regimens, 23% of the patient population showed cardiotoxicity with reduced left ventricular ejection fraction. Our results support the clinical application of plasma biomarkers and circulating miRNAs to develop a panel for early diagnosis of chemotherapy related cardiac dysfunction which will enable early detection of disease progression and management of irreversible cardiac damage.
与蒽环类药物方案治疗乳腺癌相关的心脏毒性表现会增加患者发生心肌损伤、左心室射血分数降低以及心力衰竭相关并发症的易感性。目前，尚无标准化、微创、具有成本效益且经过临床验证的程序来监测蒽环类药物治疗开始后的心脏毒性，以及检测不可逆心血管并发症的早期发作。本研究旨在创建一组与心脏毒性相关的新型生物标志物和循环miRNA，进一步评估它们与心脏损伤特异性标志物肌钙蛋白I和T的相关性，并证明乳腺癌患者心脏功能障碍的发展情况。从临床诊断为乳腺癌并接受蒽环类药物治疗的西弗吉尼亚女性身上采集的血液显示，在化疗开始3个月和6个月后，生物标志物和循环miRNA水平上调，同时心脏肌钙蛋白I和T水平升高。这些生物标志物和miRNA与肌钙蛋白升高显著相关。在接受蒽环类药物方案治疗6个月后，23%的患者出现心脏毒性，左心室射血分数降低。我们的结果支持血浆生物标志物和循环miRNA在临床中的应用，以开发一个用于早期诊断化疗相关心脏功能障碍的检测组，这将有助于早期发现疾病进展并管理不可逆的心脏损伤。
