Circulating microRNAs and Cytokines as Prognostic Biomarkers for Doxorubicin-Induced Cardiac Injury and for Evaluating the Effectiveness of an Exercise Intervention.

Authors

Prince Jeyabal
Anchit Bhagat
Fei Wang
Michael Roth
J Andrew Livingston
Susan C Gilchrist
Jose Banchs
Michelle A T Hildebrandt
Joya Chandra
Anita Deswal
Efstratios Koutroumpakis
Jian Wang
Najat C Daw
Theresa A Honey
Eugenie S Kleinerman

Publication Date

11-1-2023

Journal

Clinical Cancer Research

Abstract

Purpose: To define a set of biomarkers that can be used to identify patients at high risk of developing late doxorubicin (DOX)-induced cardiac morbidity with the goal of focused monitoring and early interventions.

Experimental design: Mice received phosphate buffered saline or DOX 2.5 mg/kg 2x/week for 2 weeks. Blood samples were obtained before and after therapy for quantification of miRNAs (6 and 24 hours), cytokines (24 hours), and troponin (24 hours, 4 and 6 weeks). Cardiac function was evaluated using echocardiography before and 24 hours after therapy. To assess the effectiveness of exercise intervention in preventing DOX-induced cardiotoxicity blood samples were collected from mice treated with DOX or DOX + exercise. Plasma samples from 13 DOX-treated patients with sarcoma were also evaluated before and 24 hours after therapy.

Results: Elevations in plasma miRNA-1, miRNA-499 and IL1α, IL1β, and IL6 were seen in DOX-treated mice with decreased ejection fraction and fractional shortening 24 hours after DOX therapy. Troponin levels were not elevated until 4 weeks after therapy. In mice treated with exercise during DOX, there was no elevation in these biomarkers and no change in cardiac function. Elevations in these biomarkers were seen in 12 of 13 patients with sarcoma treated with DOX.

Conclusions: These findings define a potential set of biomarkers to identify and predict patients at risk for developing acute and late cardiovascular diseases with the goal of focused monitoring and early intervention. Further studies are needed to confirm the predictive value of these biomarkers in late cardiotoxicity.

Keywords

Humans, Animals, Mice, Cardiotoxicity, Circulating MicroRNA, Cytokines, Prognosis, Doxorubicin, MicroRNAs, Biomarkers, Sarcoma, Troponin, Exercise Therapy, Antibiotics, Antineoplastic, microRNAs, cytokines, doxorubicin, cardiotoxicity, exercise

DOI

10.1158/1078-0432.CCR-23-1055

PMID

37651264

PMCID

PMC11370763

PubMedCentral® Posted Date

11-1-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes