Fast and Binary Assay for Predicting Radiosensitivity Based on the Theory of ATM Nucleo-Shuttling: Development, Validation, and Performance.

Abstract

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). 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. 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. 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.