High-throughput meta-analysis and validation of differentially expressed genes as potential biomarkers of ionizing radiation-response.
Biodosimetry
Bioinformatics
Human peripheral white blood cells
Microarrays
X rays irradiation
Journal
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
ISSN: 1879-0887
Titre abrégé: Radiother Oncol
Pays: Ireland
ID NLM: 8407192
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
24
01
2020
revised:
20
08
2020
accepted:
06
09
2020
pubmed:
16
9
2020
medline:
24
4
2021
entrez:
15
9
2020
Statut:
ppublish
Résumé
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. 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. We identified 275 DEGs after IR-exposure (parameters: |lfc| ≥ 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 post-irradiation. 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.
Sections du résumé
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: |lfc| ≥ 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 post-irradiation.
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.
Identifiants
pubmed: 32931891
pii: S0167-8140(20)30782-9
doi: 10.1016/j.radonc.2020.09.010
pii:
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
21-28Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.