Fast and binary assay for predicting radiosensitivity based on the nucleoshuttling of ATM protein: development, validation and performances

Abstract : Purpose The societal and clinical impact of post-radiotherapy adverse tissue events (AE) has highlighted the need of molecular parameters to predict individual radiosensitivity. Recent studies have stressed the role of the phosphorylated forms of the ATM protein (pATM) and its nucleoshuttling in response to radiation. The statistical performance of the pATM immunofluorescence assay to predict AE is promising. However, immunofluorescence requires a time-consuming amplification of cells. The purpose of this study was to develop a predictive assay based on the ELISA technique that renders faster the previous approach. Materials and methods This study was performed on 30 skin fibroblasts from 9 radioresistant and 21 AE patients. Patients were divided in 2 groups, radioresistant (toxicity grade<2) and radiosensitive (toxicity grade ≥2). The quantity of nuclear pATM molecules was assessed by ELISA method at 10 min and 1 h after 2 Gy and compared to pATM immunofluorescence data. Results The pATM ELISA data were found in quantitative agreement with the immunofluorescence ones. A ROC analysis was applied first to two data sets (a training (n=14) and a validating (n=16) one) and thereafter to the whole data with a 2-fold cross-validation method. The assay showed an AUC value higher than 0.8, a sensitivity of 0.8 and a specificity ranging from 0.75 and 1, which strongly document the predictive power of the pATM ELISA assay. Conclusion This study showed that the assessment of nuclear pATM quantity after 2 Gy via ELISA technique can be the basis of a predictive assay with the highest statistical performance among the available predictive approaches.
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Article dans une revue
International Journal of Radiation Oncology - Biology - Physics, Elsevier, 2017, 〈10.1016/j.ijrobp.2017.10.029〉
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Contributeur : Aurélien Canet <>
Soumis le : vendredi 24 novembre 2017 - 11:19:21
Dernière modification le : mercredi 12 décembre 2018 - 15:33:29

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Sandrine Pereira, Larry Bodgi, Mirlande Duclos, Aurélien Canet, Mélanie L. Ferlazzo, et al.. Fast and binary assay for predicting radiosensitivity based on the nucleoshuttling of ATM protein: development, validation and performances. International Journal of Radiation Oncology - Biology - Physics, Elsevier, 2017, 〈10.1016/j.ijrobp.2017.10.029〉. 〈hal-01647135〉

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