抗癌治疗中对心脏毒性效应具有潜在预测价值的生物标志物

doi:10.24920/003790

摘要/Abstract

摘要：

抗癌治疗在延长肿瘤患者生存期的同时,抗癌治疗引起的各种近期和远期副作用,尤其是心脏毒性显得日益突出。然而,对于恶性肿瘤患者是否会经历心血管并发症,尚无敏感度及特异度极高的早期发现和准确预测手段。炎症、纤维化和氧化应激被认为是抗癌治疗引发心脏毒性的重要机制。相对于临床症状和左室射血分数,相关的心血管生物标志物可能具有更早发现心血管功能紊乱的能力,对于及时肿瘤调整治疗方案以及患者预后评估具有更大价值。临床上,心肌肌钙蛋白T/I和脑钠肽/N-末端脑钠肽前体已被推荐用于常规心脏毒性监测,一些新的生物标志物,如可溶性肿瘤抑制因子-2、髓过氧化物酶、生长分化因子-15、半乳糖凝集素-3、内皮素-1具有潜在的研究价值。在应用于临床之前,需要大样本的试验证实其有效性,同时提高易操作性、降低成本。

关键词: 生物标志物, 心脏毒性, 抗癌治疗, 综述

Abstract:

Rapid development of anticancer treatments in recent years has greatly improved prognosis of cancer patients. However, with extension of survival time of cancer patients, various short-term and long-term side effects brought about by anticancer treatments, especially cardiotoxicity, have become increasingly prominent. Nonetheless, at present, there is few diagnostic methods with extremely high sensitivity and specificity to detect and accurately predict whether patients with anticancer treatment will experience cardiovascular complications. Inflammation, fibrosis and oxidative stress are considered to be important mechanisms involved in cardiotoxicity anticancer treatments. The cardiovascular biomarkers having the ability to predict and detect cardiovascular dysfunction earlier than clinical symptoms as well as left ventricular ejection fraction monitored by echocardiography, are of great value to timely treatment adjustment and prognosis evaluation. Cardiac troponin T/I and brain natriuretic peptide/N-terminal prohormone of brain natriuretic peptide have been routinely used in clinical practice to monitor cardiotoxicity, and some new biomarkers such as soluble suppression of tumorigenecity-2, myeloperoxidase, growth differentiation factor-15, galectin-3, endothelin-1, have potential in this area. In the future, larger-scale experimental studies are needed to provide sufficient evidences, and how to detect them quickly and at low cost is also a problem to be dealed with.

Key words: biomarkers, cardiotoxicity, anticancer treatments, review

Wei Yang, Mei Zhang. Biomarkers with Potential Predictive Value for Cardiotoxicity in Anticancer Treatments[J].Chinese Medical Sciences Journal, 2021, 36(4): 333-341.

图/表 1

Biomarkers	Physiopathologic mechanism	Clinical value for cardiotoxicity	Correlations with CVD	Advantages
cTn	Involving in acute and chronic myocardial injury and cell death	Prediction of left ventricular dysfunction; Evaluation of efficacy of cardiac protective therapy; Evaluation of prognosis	Myocarditis, HF, cardiomyopathy (including Takotsubo cardiomyopathy), aortic valve stenosis, tachyarrhythmia, pulmonary embolism, aortic dissection	Convenience of detection; Low cost
cTn				Superior diagnostic value
BNP/ NT-proBNP	Diuresis, vasodilation and regulation of human water-sodium balance; Related to endothelial function	Consistent temporal correlation between NT-proBNP and cardiotoxicity	Acute and chronic cardiac dysfunction and even HF	Convenience of detection; Low cost
sST2	Act as a decoy receptor that competes with ST2L to bind IL-33 to block its cardioprotective effect (reducing fibrosis, reducing myocardial hypertrophy, myocardial compensation and so on)	Prediction of cardiac systolic dysfunction; Risk stratification; Evaluation of prognosis	Acute and chronic cardiac dysfunction and even HF, MI	Independent predictive value for all-cause mortality; Less affected by age; Early risk stratification may be achieved at the baseline level
MPO	Play an anti-inflammatory role after catalytic reaction; Reflective of oxidative stress and inflammatory response	Early risk stratification of cardiotoxicity induced by anthracyclines	CVD such as ACS, atherosclerosis, and HF	Early risk stratification of cardiotoxicity induced by anthracyclines may be achieved at the baseline level
GDF-15	Involving in myocardial remodeling and pro-inflammation	Prediction of left ventricular dysfunction; Correlation between GDF-15 level and severity of cardiotoxicity	HFrEF, ACS, bleeding, spontaneous MI, stroke, sudden cardiac death, arrhythmia	Independent predictive value for all-cause mortality; Related to severity of cardiotoxicity
Gal-3	Involving in myocardial fibrosis	Risk stratification; Evaluation of prognosis	HFpEF and HFrEF	Independent predictive value for all-cause mortality; Contribute to risk stratification and guide treatment in the elderly
ET-1	Vasoconstriction; Positive muscle strength effect; Involving in endothelial function	Blocking ET-1 receptor can reduce cardiotoxicity of doxorubicin and play a cardioprotective role	Incident CVD	Related to cardiotoxicity induced by anthracyclines

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