Plasma Markers for Early Prediction of Radiation-Induced Myocardial Damage.

Abstract

There is no sensitive and effective method to predict radiation-induced myocardial damage (RIMD). The aim of this study was to explore effective plasma biomarkers for early prediction of RIMD after radiotherapy (RT) in lung cancer patients and in a rat model. Biomarker levels were measured in plasma samples collected before and after thoracic RT from 17 lung cancer patients. For the animal model, a single radiation dose of 40 Gy was delivered to the cardiac apex of female Wistar rats. Control rats received sham irradiation (0 Gy). Dynamic plasma biomarker detection and histopathological analysis to confirm RIMD were performed in rats up to 6 months after RT. In lung cancer patients, the plasma caspase-3 concentration was significantly increased after thoracic RT (P = 0.0479), with increasing but nonsignificant trends observed for caspase-1, CCL2, vascular endothelial growth factor (VEGF), interleukin-1β, and IL-6 (P > 0.05). Changes in caspase-3, VEGF, and IL-6 correlated significantly with mean heart dose (P < 0.05). In the RIMD rat model, caspase-1, caspase-3, CCl-2, VEGF, CCl-5, and TGF-β1 levels were significantly elevated in the first week post-RT (P < 0.05), which was earlier than pathological changes. Myocardial tissue of the RIMD rats also showed significant macrophage infiltration at 1 month (P < 0.01) and fibrosis at 6 months postradiation (P < 0.0001). Macrophage infiltration correlated significantly with plasma caspase-3, CCL2, CCL5, VEGF, and TGF-β1 levels from 3 weeks to 2 months post-RT. Increased plasma caspase-1, caspase-3, CCl-2, and VEGF levels were detected before RIMD-related pathological changes, indicating their clinical potential as biomarkers for early prediction of RIMD.