High-throughput meta-analysis and validation of differentially expressed genes as potential biomarkers of ionizing radiation-response

Background and purpose: The high-throughput analysis of gene expression in ionizing radiation (IR)exposed human peripheral white blood cells (WBC) has emerged as a novel method for biodosimetry markers detection. We aimed to detect IR-exposure differential expressed genes (DEGs) as potential predictive biomarkers for biodosimetry and radioinduced-response. Materials and methods: We performed a meta-analysis of raw data from public microarrays of ex vivo low linear energy transfer-irradiated human peripheral WBC. Functional enrichment and transcription factors (TF) detection from resulting DEGs were assessed. Six selected DEGs among studies were validated by qRT-PCR on mRNA from human peripheral blood samples from nine healthy human donors 24 h after ex vivo X-rays-irradiation. Results: We identified 275 DEGs after IR-exposure (parameters: vertical bar lfc vertical bar >= 0.7, q value <0.05), enriched in processes such as regulation after IR-exposure, DNA damage checkpoint, signal transduction by p53 and mitotic cell cycle checkpoint. Among these DEGs, DRAM1, NUDT15, PCNA, PLK2 and TIGAR were selected for qRT-PCR validation. Their expression levels significantly increased at 1-4 Gy respect to non-irradiated controls. Particularly, PCNA increased dose dependently. Curiously, TCF4 (Entrez Gene: 6925), detected as overrepresented TF in the radioinduced DEGs set, significantly decreased postirradiation. Conclusion: These six DEGs show potential to be proposed as candidates for IR-exposure biomarkers, considering their observed molecular radioinduced-response. Among them, TCF4, bioinformatically detected, was validated herein as an IR-responsive gene. (C) 2020 Elsevier B.V. All rights reserved. Radiotherapy and Oncology

Automated summary

The study identified potential predictive biomarkers for biodosimetry and radioinduced-response through high-throughput gene expression analysis in IR-exposed human peripheral white blood cells. Six selected DEGs were validated by qRT-PCR, showing significant upregulation post IR-exposure, with PCNA expression levels increasing dose-dependently. Notably, TCF4 was bioinformatically detected as an overrepresented TF in the radioinduced DEGs set and was validated as an IR-responsive gene post-irradiation.