Identification of radiosensitivity predictive genes in gastric cancer cell line using gene expression profiling

Abstract

Abstract Background: In the post-genome era, the development of a radiation sensitivity predictive assay is significant as it could lead to better patient and dose selection in radiotherapy. Methods: To identify radiosensitivity predictive genes in gastric cancer cells, 12 gastric and 4 colorectal cancer cell lines were used. Oligonucleotide microarray was performed using a human oligo chip containing 22,740 oligonucleotide probes of 70 bases with a reference design before radiation. Clonogenic survival assays with 2Gy of radiation were performed and survival fraction at 2 Gy (SF2) was measured. Differentially expressed genes were identified through Significant analysis of microarrays (SAM) between radiosensitive and radioresistant cell lines and functional study through Ingenuity pathway analysis was conducted. Results: According to SF2, SNU-638 (0.127±0.038), MKN-1 (0.143±0.032), and HCT-116 (0.313±0.034) were classified as radiosensitive cells, whereas YCC-2 (0.609±0.046), YCC-16 (0.62±0.091), HT29 (0.641±0.070), and YCC-7 (0.667±0.192) were determined as radioresistant cells. Eighty-two up-regulated and one hundred and forty-two down-regulated genes were identified in radiosensitive cell lines compared to radioresistant cell lines. Cell death (43 genes), cellular growth and proliferation (36 genes), cell-to-cell signaling (16 genes), cell cycle (13 genes), and DNA repair (6 genes) were related with identified gene set. Genetic network via TGFB1 and TP53 showed important role in radiosensitivity. Conclusions: Our results suggest that identified genes are candidates for radiosensitivity biomarker discovery and in vitro clonogenic assay with expression analysis may assist to predict responsiveness to radiotherapy.