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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Lacombe, Jérôme Brengues, Muriel Mangé, Alain Bourgier, Céline Gourgou, Sophie Pèlegrin, André Ozsahin, Mahmut Solassol, Jérôme Azria, David |
| Abstract | Background 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. Methods 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. Results 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+). Conclusion 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. |
| Related Links | https://ro-journal.biomedcentral.com/counter/pdf/10.1186/s13014-019-1351-8.pdf |
| Ending Page | 11 |
| Page Count | 11 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/s13014-019-1351-8 |
| Journal | Radiation Oncology |
| Issue Number | 1 |
| Volume Number | 14 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2019-08-09 |
| Access Restriction | Open |
| Subject Keyword | Cancer Research Oncology Radiotherapy Imaging Radiology Normal tissue radiotoxicity AK2 Radiation-induced breast fibrosis Radiosensitivity Proteomics NADPH oxidases |
| Content Type | Text |
| Resource Type | Article |
| Subject | Radiology, Nuclear Medicine and Imaging Oncology |
| Journal Impact Factor | 3.3/2023 |
| 5-Year Journal Impact Factor | 3.6/2023 |
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