Anthracyclines are anti-neoplastic drugs presenting cardiotoxicity as a side effect. Cardiac troponins (cTn) and echocardiography are currently used to assess cardiac damage and dysfunction, but early biomarkers identifying patients in need of preventive treatments remain a partially met need. Circulating microRNAs (miRNAs) represent good candidates, so we investigated their possible roles as predictors of troponin elevation upon anthracycline treatment. Eighty-eight female breast cancer patients administered with doxorubicin (DOX) or epirubicin (EPI) were divided into four groups basing on drug type and cTn positive (cTn+) or negative (cTn-) levels: DOX cTn-, DOX cTn+, EPI cTn- and EPI cTn+. Blood was collected at baseline, during treatment, and at follow-up. We identified plasma miRNAs of interest by OpenArray screening and single assay validation. Our results showed miR-122-5p, miR-499a-5p and miR-885-5p dysregulation in DOX patients at T0, identifying a signature separating, with good accuracy, DOX cTn- from DOX cTn+. No miRNAs showed differential expression in EPI subjects. Conversely, an anthracycline-mediated modulation (regardless of cTn) was observed for miR-34a-5p, -122-5p and -885-5p. Our study indicates specific circulating miRNAs as possible prediction markers for cardiac troponin perturbation upon anthracycline treatment. Indeed, our findings hint at the possible future use of plasma miRNAs to predict the cardiac responsiveness of patients to different anticancer agents.

译文

蒽环类药物是抗肿瘤药物,具有心脏毒性作为副作用。心肌肌钙蛋白 (cTn) 和超声心动图目前用于评估心脏损伤和功能障碍,但早期识别需要预防性治疗的患者的生物标志物仍然是部分满足的需求。循环microrna (mirna) 代表了良好的候选者,因此我们研究了它们作为蒽环类药物治疗后肌钙蛋白升高的预测因子的可能作用。根据药物类型和cTn阳性 (cTn) 或阴性 (cTn-) 水平将88例接受阿霉素 (DOX) 或表柔比星 (EPI) 的女性乳腺癌患者分为四组: DOX cTn-,DOX cTn,EPI cTn-和EPI cTn。在基线,治疗期间和随访时收集血液。我们通过开放阵列筛选和单分析验证鉴定了目标血浆miRNAs。我们的结果显示,在T0时,DOX患者的miR-122-5p,miR-499a-5p和miR-885-5p失调,从而确定了将DOX cTn-与DOX cTn分离的准确性良好的特征。在EPI受试者中没有mirna显示差异表达。相反,对于miR-34a-5p,-122-5p和-885-5p观察到蒽环类药物介导的调节 (与cTn无关)。我们的研究表明,特定的循环mirna可能是蒽环类药物治疗后心肌肌钙蛋白扰动的预测标志物。实际上,我们的发现暗示了将来可能使用血浆mirna来预测患者对不同抗癌药物的心脏反应性。

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