Chałubińska-Fendler Justyna, Nowicka Zuzanna, Dróżdż Izabela, Graczyk Łukasz, Piotrowski Grzegorz, Tomasik Bartłomiej, Spych Michał, Fijuth Jacek, Papis-Ubych Anna, Kędzierawski Piotr, Kozono David, Fendler Wojciech
Department of Radiotherapy, Military Institute of Medicine - National Research Institute, Warsaw, Poland.
Department of Biostatistics and Translational Medicine, Medical University of Łódź, Łódź, Poland.
Front Oncol. 2023 May 18;13:1150979. doi: 10.3389/fonc.2023.1150979. eCollection 2023.
Patients treated with radiotherapy to the chest region are at risk of cardiac sequelae, however, identification of those with greatest risk of complications remains difficult. Here, we sought to determine whether short-term changes in circulating miRNA expression are related to measures of cardiac dysfunction in follow-up.
Two parallel patient cohorts were enrolled and followed up for 3 years after completion of RT to treat left-sided breast cancer. In the primary group (N=28) we used a a panel of 752 miRNAs to identify miRNAs associated with radiation and cardiac indices at follow up. In the second, independent cohort (N=56) we validated those candidate miRNAs with a targeted qPCR panel. In both cohorts. serum samples were collected before RT, 24h after the last dose and 1 month after RT; cardiac echocardiography was performed 2.5-3 year after RT.
Seven miRNAs in the primary group showed marked changes in serum miRNAs immediately after RT compared to baseline and associations with cardiopulmonary dose-volume histogram metrics. Among those miRNAs: miR-15b-5p, miR-22-3p, miR-424-5p and miR-451a were confirmed to show significant decrease of expression 24 hours post-RT in the validation cohort. Moreover, miR-29c, miR-451 and miR-424 were correlated with the end-diastolic diameter of the left ventricle, which was also confirmed in multivariable analysis adjusting for RT-associated factors.
We identified a subset of circulating miRNAs predictive for cardiac function impairment in patients treated for left-sided breast cancer, although longer clinical observation could determine if these can be used to predict major clinical endpoints.
接受胸部放疗的患者有发生心脏后遗症的风险，然而，识别那些并发症风险最高的患者仍然很困难。在此，我们试图确定循环miRNA表达的短期变化是否与随访中的心脏功能障碍指标相关。
招募了两个平行的患者队列，并在完成左侧乳腺癌放疗后进行了3年的随访。在主要队列（N = 28）中，我们使用一组752种miRNA来识别与放疗及随访时心脏指标相关的miRNA。在第二个独立队列（N = 56）中，我们用靶向qPCR面板验证了那些候选miRNA。在两个队列中，放疗前、最后一剂放疗后24小时和放疗后1个月采集血清样本；放疗后2.5 - 3年进行心脏超声心动图检查。
主要队列中的7种miRNA显示，与基线相比，放疗后血清miRNA立即出现明显变化，并与心肺剂量 - 体积直方图指标相关。在这些miRNA中：miR - 15b - 5p、miR - 22 - 3p、miR - 424 - 5p和miR - 451a在验证队列中被证实放疗后24小时表达显著降低。此外，miR - 29c、miR - 451和miR - 424与左心室舒张末期直径相关，这在对放疗相关因素进行调整的多变量分析中也得到了证实。
我们在接受左侧乳腺癌治疗的患者中鉴定出了一组可预测心脏功能损害的循环miRNA，尽管更长时间的临床观察才能确定这些miRNA是否可用于预测主要临床终点。
