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

Sandrine Pereira 1 Larry Bodgi 1 Mirlande Duclos 1 Aurélien Canet 1, 2, 3 Mélanie L. Ferlazzo 1 Clément Devic 1 Adeline Granzotto 1 Sophie Deneuve 1 Guillaume Vogin 1 Nicolas Foray 1
2 DRACULA - Multi-scale modelling of cell dynamics : application to hematopoiesis
CGPhiMC - Centre de génétique et de physiologie moléculaire et cellulaire, Inria Grenoble - Rhône-Alpes, ICJ - Institut Camille Jordan [Villeurbanne]
3 MMCS - Modélisation mathématique, calcul scientifique
ICJ - Institut Camille Jordan [Villeurbanne]
Abstract : PurposeThe 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 methodsThis 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.ResultsThe 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.ConclusionThis 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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https://hal.inria.fr/hal-01647135
Contributor : Aurélien Canet <>
Submitted on : Friday, November 24, 2017 - 11:19:21 AM
Last modification on : Monday, June 14, 2021 - 1:58:05 PM

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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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