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Published on: September 5, 2017
microRNA blood signature for localized radiation injury
Lucie Ancel1, Olivier Gabillot1, Chloé Szurewsky1
1Radiobiology and Regenerative Medicine Research Service, Radiobiology of Accidental Exposure Laboratory, IRSN PSE-SANTE/SERAMED/LRAcc, 31 av de la Division Leclerc, 92260, Fontenay-aux-Roses, France.
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.
Insights
Researchers identified a signature of eight circulating microRNAs (miRNAs) in mice that can diagnose local radiation injury (LRI) severity. This discovery offers potential for early LRI diagnosis and prognosis using blood-based biomarkers.
Area of Science:
- Radiation Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Radiological accidents can cause severe local radiation injury (LRI) affecting skin and underlying tissues.
- Early diagnosis of LRI is critical for effective victim management.
- Circulating microRNAs (miRNAs) show promise as biomarkers for radiation-induced hematological defects.
Purpose of the Study:
- To identify a blood miRNA signature for diagnosing local radiation injury (LRI) severity.
- To investigate circulating miRNAs as potential biomarkers for LRI in a preclinical mouse model.
Main Methods:
- Utilized a hindlimb irradiation mouse model with varying X-ray doses to induce LRI.
- Performed broad-spectrum plasma miRNA profiling followed by targeted validation in two independent cohorts.
- Employed multivariate sparse partial least square discriminant analysis to identify a miRNA signature.
Main Results:
- Identified a panel of eight circulating miRNAs capable of distinguishing LRI severity in mice.
- The identified miRNAs are associated with whole-body irradiation, inflammation, and skin diseases.
- The miRNA signature effectively segregated mice based on the severity of induced local radiation injury.
Conclusions:
- Circulating miRNAs can serve as effective molecular biomarkers for the prognosis and diagnosis of local radiation injury.
- The identified eight-miRNA signature holds potential for early LRI detection and patient stratification.
- This study supports the development of non-invasive diagnostic tools for radiation-related injuries.
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