Radiation-induced circulating microRNAs linked to echocardiography parameters after radiotherapy

Abstract

Introduction: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: biomarkers; breast cancer; echocardiography; microRNA; radiation-induced cardiac toxicity.