Quantitative proteomic analysis reveals AK2 as potential biomarker for late normal tissue radiotoxicity.

Details

Serval ID
serval:BIB_5717C8853286
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Quantitative proteomic analysis reveals AK2 as potential biomarker for late normal tissue radiotoxicity.
Journal
Radiation oncology
Author(s)
Lacombe J., Brengues M., Mangé A., Bourgier C., Gourgou S., Pèlegrin A., Ozsahin M., Solassol J., Azria D.
ISSN
1748-717X (Electronic)
ISSN-L
1748-717X
Publication state
Published
Issued date
09/08/2019
Peer-reviewed
Oui
Volume
14
Number
1
Pages
142
Language
english
Notes
Publication types: Journal Article ; Multicenter Study
Publication Status: epublish
Abstract
Biomarkers for predicting late normal tissue toxicity to radiotherapy are necessary to personalize treatments and to optimize clinical benefit. Many radiogenomic studies have been published on this topic. Conversely, proteomics approaches are not much developed, despite their advantages.
We used the isobaric tags for relative and absolute quantitation (iTRAQ) proteomic approach to analyze differences in protein expression levels in ex-vivo irradiated (8 Gy) T lymphocytes from patients with grade ≥ 2 radiation-induced breast fibrosis (grade ≥ 2 bf+) and patients with grade < 2 bf + after curative intent radiotherapy. Patients were selected from two prospective clinical trials (COHORT and PHRC 2005) and were used as discovery and confirmation cohorts.
Among the 1979 quantified proteins, 23 fulfilled our stringent biological criteria. Immunoblotting analysis of four of these candidate proteins (adenylate kinase 2, AK2; annexin A1; heat shock cognate 71 kDa protein; and isocitrate dehydrogenase 2) confirmed AK2 overexpression in 8 Gy-irradiated T lymphocytes from patients with grade ≥ 2 bf + compared with patients with grade < 2 bf+. As these candidate proteins are involved in oxidative stress regulation, we also evaluated radiation-induced reactive oxygen species (ROS) production in peripheral blood mononuclear cells from patients with grade ≥ 2 bf + and grade < 2 bf+. Total ROS level, and especially superoxide anion level, increased upon ex-vivo 8 Gy-irradiation in all patients. Analysis of NADPH oxidases (NOXs), a major source of superoxide ion in the cell, showed a significant increase of NOX4 mRNA and protein levels after irradiation in both patient groups. Conversely, only NOX4 mRNA level was significantly different between groups (grade ≥ 2 bf + and grade < 2 bf+).
These findings identify AK2 as a potential radiosensitivity candidate biomarker. Overall, our proteomic approach highlights the important role of oxidative stress in late radiation-induced toxicity, and paves the way for additional studies on NOXs and superoxide ion metabolism.
Keywords
Adenylate Kinase/metabolism, Biomarkers/metabolism, Breast/metabolism, Breast/radiation effects, Breast Neoplasms/radiotherapy, Female, Fibrosis/etiology, Fibrosis/metabolism, Fibrosis/pathology, Humans, Organs at Risk/radiation effects, Prognosis, Prospective Studies, Proteome/analysis, Radiation Injuries/etiology, Radiation Injuries/metabolism, Radiation Injuries/pathology, Radiation Tolerance, Radiotherapy/adverse effects, Reactive Oxygen Species/metabolism, T-Lymphocytes/metabolism, T-Lymphocytes/pathology, T-Lymphocytes/radiation effects, AK2, NADPH oxidases, Normal tissue radiotoxicity, Proteomics, Radiation-induced breast fibrosis, Radiosensitivity, Radiotherapy
Pubmed
Web of science
Open Access
Yes
Create date
19/08/2019 16:25
Last modification date
08/06/2020 5:26
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