Abstract
A radiological accident, whether from industrial, medical, or malicious origin, may result in localized exposure to high doses of ionizing radiations, leading to the development of local radiation injury (LRI), that may evolve toward deep ulceration and necrosis of the skin and underlying tissues. Early diagnosis is therefore crucial to facilitate identification and management of LRI victims. Circulating microRNAs (miRNA) have been studied as potential diagnostic biomarkers of several diseases including hematological defects following whole-body irradiation (WBI). This study aims to identify a blood miRNA signature associated with LRI in a preclinical C57BL/6J mouse model of hindlimb irradiation using different 10-MV X-ray doses that lead to injuries of different severities. To this end, we first performed broad-spectrum plasma miRNA profiling, followed by a targeted validation step, on two independent animal cohorts. Using a multivariate sparse partial least square discriminant analysis, we identified a panel of eight circulating miRNAs able to segregate mice according to LRI severity. Interestingly, these miRNAs were previously associated with WBI (miR-150-5p, miR-342-3p, miR-146a-5p), inflammation (miR-18a-5p, miR-148b-3p, miR-532-5p) and skin diseases (miR-139-5p, miR-195-5p). Our results suggest the use of circulating miRNAs as suitable molecular biomarkers for LRI prognosis and diagnosis.