Sandrine Pereira1, Larry Bodgi1, Mirlande Duclos1, Aurélien Canet2, Mélanie L Ferlazzo3, Clément Devic3, Adeline Granzotto3, Sophie Deneuve4, Guillaume Vogin3, Nicolas Foray5. 1. Institut National de la Santé et de la Recherche Médicale, Radiobiology Group, Cancer Research Centre of Lyon, Unité Mixte de Recherche 1052, Institut National de la Santé et de la Recherche Médicale, Lyon, France; Neolys Diagnostics, Lyon, France. 2. Institut National de la Santé et de la Recherche Médicale, Radiobiology Group, Cancer Research Centre of Lyon, Unité Mixte de Recherche 1052, Institut National de la Santé et de la Recherche Médicale, Lyon, France; Neolys Diagnostics, Lyon, France; Université de Lyon, Institut Camille Jordan, Université de Lyon, Villeurbanne, France. 3. Institut National de la Santé et de la Recherche Médicale, Radiobiology Group, Cancer Research Centre of Lyon, Unité Mixte de Recherche 1052, Institut National de la Santé et de la Recherche Médicale, Lyon, France. 4. Centre Anti-cancer Léon-Bérard, Lyon, France. 5. Institut National de la Santé et de la Recherche Médicale, Radiobiology Group, Cancer Research Centre of Lyon, Unité Mixte de Recherche 1052, Institut National de la Santé et de la Recherche Médicale, Lyon, France. Electronic address: nicolas.foray@inserm.fr.
Abstract
PURPOSE: To examine the possibility of predicting clinical radiosensitivity by quantifying the nuclear forms of autophosphorylated ATM protein (pATM) via a specific enzyme-linked immunosorbent assay (ELISA). METHODS AND MATERIALS: This study was performed on 30 skin fibroblasts from 9 radioresistant patients and 21 patients with adverse tissue reaction events. Patients were divided into 2 groups: radioresistant (toxicity grade <2) and radiosensitive (toxicity grade ≥2). The quantity of nuclear pATM molecules was assessed by the ELISA method at 10 minutes and 1 hour after 2 Gy and compared with pATM immunofluorescence data. RESULTS: The pATM ELISA data were in quantitative agreement with the immunofluorescence data. A receiver operating characteristic analysis was applied first to 2 data sets (a training set [n=14] and a validating [n=16] set) and thereafter to all the data with a 2-fold cross-validation method. The assay showed an area under the curve value higher than 0.8, a sensitivity of 0.8, and a specificity ranging from 0.75 to 1, which strongly documents the predictive power of the pATM ELISA. CONCLUSION: This study showed that the assessment of nuclear pATM quantity after 2 Gy via an ELISA technique can be the basis of a predictive assay with the highest statistical performance among the available predictive approaches.
PURPOSE: To examine the possibility of predicting clinical radiosensitivity by quantifying the nuclear forms of autophosphorylated ATM protein (pATM) via a specific enzyme-linked immunosorbent assay (ELISA). METHODS AND MATERIALS: This study was performed on 30 skin fibroblasts from 9 radioresistant patients and 21 patients with adverse tissue reaction events. Patients were divided into 2 groups: radioresistant (toxicity grade <2) and radiosensitive (toxicity grade ≥2). The quantity of nuclear pATM molecules was assessed by the ELISA method at 10 minutes and 1 hour after 2 Gy and compared with pATM immunofluorescence data. RESULTS: The pATM ELISA data were in quantitative agreement with the immunofluorescence data. A receiver operating characteristic analysis was applied first to 2 data sets (a training set [n=14] and a validating [n=16] set) and thereafter to all the data with a 2-fold cross-validation method. The assay showed an area under the curve value higher than 0.8, a sensitivity of 0.8, and a specificity ranging from 0.75 to 1, which strongly documents the predictive power of the pATM ELISA. CONCLUSION: This study showed that the assessment of nuclear pATM quantity after 2 Gy via an ELISA technique can be the basis of a predictive assay with the highest statistical performance among the available predictive approaches.
Authors: K E Applegate; W Rühm; A Wojcik; M Bourguignon; A Brenner; K Hamasaki; T Imai; M Imaizumi; T Imaoka; S Kakinuma; T Kamada; N Nishimura; N Okonogi; K Ozasa; C E Rübe; A Sadakane; R Sakata; Y Shimada; K Yoshida; S Bouffler Journal: Radiat Environ Biophys Date: 2020-03-07 Impact factor: 1.925
Authors: Salvatore Terrazzino; Sarah Cargnin; Letizia Deantonio; Carla Pisani; Laura Masini; Pier Luigi Canonico; Armando A Genazzani; Marco Krengli Journal: PLoS One Date: 2019-11-22 Impact factor: 3.240