Identification of a radiosensitivity gene signature in gastric cancer cells using microarray analysis

Abstract

Background: Prediction of response prior to radiotherapy is future direction of radiotherapy and identification of druggable targets in radiotherapy could overcome resistance. In order to identify a radiosensitivity gene signature and elucidate relevant signaling pathways, microarrays using gastric cancer cells were analyzed before radiotherapy.Methods: Oligonucleotide microarray containing 22,740 probes was performed using twelve gastric cancer cells before radiation. Clonogenic assays with 2Gy of radiation were performed and survival fraction at 2 Gy (SF2) was measured as surrogate marker for radiosensitivity. Differentially expressed genes were identified between radiosensitive and radioresistant cells and gene set analysis was performed. Pathway analysis using Ingenuity pathway analysis (IPA) was conducted. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed for validation.Results: In individual gene analysis, 68 genes were identified as a radiosensitivity gene signature. Identified genes were interact with VEGF, AKT, TGF-β, NFκB, ERK, PI3K, HIF1A, MDM2, TGFB1 and TP53 in IPA. Functions associated with genetic networks were cellular growth and proliferation, cellular movement, and cell cycle. Gene set analysis using entire genes enriched several pathways including Akt signaling. qRT-PCR results were well correlated with microarray experiments (the Pearson correlation coefficient, 0.91-0.99).Conclusion: We first identified 68-radiosensitivity gene signature in gastric cancer cells. Akt signaling pathway could be druggable target for radiosensitization in gastric cancer. We suggest that this analysis could elucidate targets for radiosensitivity biomarker discovery and the identified genes and signaling pathways could be served as potential targets in radiotherapy.