IDENTIFICATION AND CHARACTERIZATION OF DIFFERENTIAL GENE EXPRESSION IN WHITE BLOOD CELLS EXPOSED TO IONIZING RADIATION

VANESA BIOLATTI; NICOLAS BELLORA; IRENE LAURA IBAÑEZ

Buenos Aires

Congreso; Joint Meeting of Bioscience Societies 2017; 2017

Argentine Society of Clinical Investigation (SAIC)

The analysis of gene expression in blood cells has been emergedas a novel method for biodosimetry marker detection. The differentialexpressed genes could predict the clinical outcome of patientsand guide the prevention, early diagnosis and treatment of ionizingradiation induced damage, improving traditional approaches. Theaim of this study was to perform a meta-analysis of expression microarraydata of irradiated blood cells in order to identify differentiallyexpressed genes with overlapping among studies, which could beproposed as biomarkers of ionizing radiation exposure at 2 Gy and24 h post-exposure. Data of four expression microarrays obtainedfrom Gene Expression Omnibus (GEO) were evaluated by using theR programming language and Bioconductor packages. Differentialgene expression was evaluated by Limma (parameters: lfc=1 andp<0.005). The functional classification was done with the MolecularSignature Database from Gene Set Enrichment Analysis (FDR<0.05)and Database for Annotation, Visualization and Integrated Discovery(DAVID). The iRegulon database was used to identify transcriptionfactors (TFs) as master regulators and the gene networks werevisualized by GeneMANIA. Nine differentially expressed genes(E2F7, PLK2, TCF4, DRAM1, POLR2A, HRK, NUDT15, C12orf15and GADD45A) were identified (lfc<0.5 and p<0.001) for further validationusing quantitative PCR. These genes are associated withregulation after exposure to ionizing radiation, p53 pathway, cellcycle checkpoint involved in G1/S transition, cell cycle arrest andprocesses induced by the detection of DNA damage. Besides, E2F7and TCF4 were detected as master regulators TFs with corepressoractivity. In conclusion, we identified nine genes which could be relevantas biomarkers of ionizing radiation exposure for biodosimetrystudies. Further studies on these genes will relevant to understandthe patterns of gene expression in response to ionizing radiation inArgentine subjects.