Development and Validation of a Novel Radiosensitivity Signature in @entity1 XXXX .

@entity1 @entity5 @entity0 @entity1161
PURPOSE: An unmet clinical need in @entity0 management is the accurate identification of @entity1 who will benefit from adjuvant radiotherapy. We hypothesized that integration of postradiation clonogenic survival data with gene expression data across @entity0 cell (BCC) lines would generate a @entity1161 ( @entity1161 ) and identify @entity1 with @entity5 refractive to conventional therapy. EXPERIMENTAL DESIGN: Using clonogenic survival assays, we identified the surviving fraction (SF-2Gy) after radiation across a range of BCC lines. Intrinsic radiosensitivity was correlated to gene expression using Spearman correlation. Functional analysis was performed in vitro, and enriched biologic concepts were identified. The @entity1161 was generated using a Random Forest model and was refined, cross-validated, and independently validated in additional @entity0 datasets. RESULTS: Clonogenic survival identifies a range of radiosensitivity in @entity1 BCC lines (SF-2Gy 77%-17%) with no significant correlation to the @entity0 subtypes. One hundred forty-seven genes were correlated with radiosensitivity. Functional analysis of @entity1161 genes identifies previously unreported radioresistance-associated genes. @entity1161 was trained, cross-validated, and further refined to 51 genes that were enriched for concepts involving cell-cycle arrest and DNA damage response. @entity1161 was validated in an independent dataset and was the most significant factor in predicting local recurrence on multivariate analysis, outperfoming all clinically used clinicopathologic features. CONCLUSIONS: We derive a @entity1 @entity0 -specific @entity1161 with biologic relevance and validate this signature for prediction of locoregional recurrence. By identifying @entity1 with @entity5 refractory to standard radiation this signature has the potential to allow for personalization of radiotherapy.
