Plasma metabolite biomarkers predictive of radiation induced cardiotoxicity.
Keith Unger, Yaoxiang Li, Celine Yeh, Ana Barac, Monvadi B Srichai, Elizabeth A Ballew, Michael Girgis, Meth Jayatilake, Vijayalakshmi Sridharan, Marjan Boerma, Amrita K Cheema
Author Information
Keith Unger: Department of Radiation Medicine, MedStar Georgetown University Hospital, Washington D.C., United States.
Yaoxiang Li: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington D.C., United States.
Celine Yeh: Department of Radiation Medicine, MedStar Georgetown University Hospital, Washington D.C., United States.
Ana Barac: Department of Cardiology, MedStar Georgetown University Hospital and Medstar Washington Hospital Center, Washington D.C., United States.
Monvadi B Srichai: Department of Cardiology, MedStar Georgetown University Hospital and Medstar Washington Hospital Center, Washington D.C., United States; Department of Radiology, Medstar Georgetown University Hospital, Washington D.C., United States.
Elizabeth A Ballew: Department of Radiation Medicine, MedStar Georgetown University Hospital, Washington D.C., United States.
Michael Girgis: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington D.C., United States.
Meth Jayatilake: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington D.C., United States.
Vijayalakshmi Sridharan: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, United States.
Marjan Boerma: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, United States.
Amrita K Cheema: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington D.C., United States; Department of Biochemistry, Molecular and Cellular Biology, Georgetown University, Georgetown University Medical Center, Washington D.C., United States. Electronic address: akc27@georgetown.edu.
PURPOSE: Although advancements in cancer treatments using radiation therapy (RT) have led to improved outcomes, radiation-induced heart disease (RIHD) remains a significant source of morbidity and mortality in survivors of cancers in the chest. Currently, there are no diagnostic tests in clinical use due to a lack of understanding of the natural history and mechanisms of RIHD development. Few studies have examined the utility of using metabolomics to prospectively identify cancer survivors who are at risk of developing cardiotoxicity. METHODS: We analyzed plasma and left ventricle heart tissue samples collected from a cohort of male Sprague Dawley (SD) rats that were either sham irradiated or received fractionated doses (9 Gy per day × 5 days) of targeted X-ray radiation to the heart. Metabolomic and lipidomic analyses were utilized as a correlative approach for delineation of novel biomarkers associated with radiation-induced cardiac toxicity. Additionally, we used high-resolution mass spectrometry to examine the metabolomic profiles of plasma samples obtained from patients receiving high dose thoracic RT for esophageal cancer. RESULTS: Metabolic alterations in the rat model and patient plasma profiles, showed commonalities of radiation response that included steroid hormone biosynthesis and vitamin E metabolism. Alterations in patient plasma profiles were used to develop classification algorithms predictive of patients at risk of developing RIHD. CONCLUSION: Herein, we report the feasibility of developing a metabolomics-based biomarker panel that is associated with adverse outcomes of cardiac function in patients who received RT for the treatment of esophageal cancer.
