There are two limitations to this study. First, we used NCI 60 cancer cell lines to identify common radiosensi tivity signatures Sorafenib Tosylate structure regardless of cell type. Defining com mon radiosensitive mechanisms not affected by cell type is helpful, but the actual cellular response in biological validation might differ among cell types. However, we adjusted for this effect using statistical methods. Adjusted correlation coefficients were similar to correl ation coefficients before adjustment. Second, although we identified a gene signature using four microarray array platforms, using not only mRNA expression, but also comparing DNA sequences or protein expres sion would give a comprehensive analysis of the radiosen sitivity mechanism. Conclusions A common radiosensitivity gene signature was identi fied that involved 31 genes.

Their major functions were in the cell cycle, cell junctions, and cell adhesion. Adhesion related molecules were enriched in the integ rin signaling pathway and could be targeted for radio sensitization. This is the first study to use multiple microarray platforms to study radiosensitivity, and might provide insights in elucidating novel therapeutic targets and common radiosensitivity mechanisms re gardless of cell type. Methods Radiosensitivity profiling and mRNA expression profiling Radiosensitivity profiling was defined as the survival frac tion at 2 Gy radiation. Radiosensitivity signature genes were identified from previously published SF2 data on radiosensitivity profiling and gene expression profiling of the NCI 60 cell line panel.

Briefly, the cells had been plated and radiated with 2 Gy of x rays. After fixation, colonies of over 50 cells were calculated. SF2 was determined by the formula. SF2 ranged from 0 to 1, with a lower SF2 representing more radiosensitivity. Gene expression profiling data using the NCI 60 cancer cell line panel was from cDNA and two color arrays, and HU 6800, HG U133, and HG U95 Affymetrix microarrays, and obtained from Cellminer and NCI60. html. The gene expression data were acquired from the National Center for Biotechnology Informa tion Gene Expression Omnibus. Gene annotations were obtained from the SOURCE database After gene annotation, we matched gene symbols among the four microarray platforms.

For AV-951 normalization, robust multiarray analysis was used for normalizing Affymetrix gene chips and the linear models for microarray data package was used with the R program for normalizing the two color array. Missing values were imputed using the K nearest neighbor method. All acquired microarray data were from experiments using cells in the unirra diated status. Identification of a common radiosensitive gene signature A radiosensitive signature gene was defined as a gene whose mRNA expression correlated with SF2. SF2 was defined as a continuous variable. Gene selection was performed using SAM.