| Luo Hui,Wang Liuxiang,Ron Leavitt,et al.Proteomic analysis of differentially expressed proteins in mice plasma following FLASH and conventional dose rate whole-lung irradiation[J].Chinese Journal of Radiological Medicine and Protection,2025,45(10):941-948 |
| Proteomic analysis of differentially expressed proteins in mice plasma following FLASH and conventional dose rate whole-lung irradiation |
| Received:September 23, 2024 |
| DOI：10.3760/cma.j.cn112271-20240923-00373 |
| KeyWords:FLASH irradiation Tumor control Acute radiation-induced lung injury Proteomics |
| FundProject:河南省科技攻关计划(212102310619) |
| Author Name | Affiliation | E-mail | | Luo Hui | Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China | | | Wang Liuxiang | Academy of Medical Science, Zhengzhou University, Zhengzhou 450001, China | | | Ron Leavitt | Department of Radiation Oncology, Lausanne University Hospital, Lausanne 1002, Switzerland | | | Jackie Romero | Department of Radiation Oncology, Lausanne University Hospital, Lausanne 1002, Switzerland | | | Marie-Catherine Vozenin | Department of Radiation Oncology, Lausanne University Hospital, Lausanne 1002, Switzerland | | | Aymeric Almeida | Department of Radiation Oncology, Lausanne University Hospital, Lausanne 1002, Switzerland | | | Yang Chengliang | Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China | | | Li Na | School of Radiology, Shandong First Medical University, Shandong Academy of Medical Sciences, Tai'an 271021, China | | | Wang Xuenan | School of Radiology, Shandong First Medical University, Shandong Academy of Medical Sciences, Tai'an 271021, China | | | Mao Ronghu | Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China | | | Ma Leijie | Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China | | | Lei Hongchang | Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China | | | Ge Hong | Department of Radiation Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China | zlyygehong0199@zzu.edu.cn |
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| Abstract:: |
| Objective To observe the tumor control and the degree of radiation-induced lung injury (RILI) between FLASH irradiation and conventional dose rate (CONV) irradiation, and compare the changes in plasma proteomic profiles of mice following whole-lung FLASH and CONV irradiation using proteomics method. Methods A mouse model with metastatic lung cancer was established. After whole-lung irradiation, changes in normal lung capacity were monitored using CT scans. Then, a RILI model was constructed to examine pathological alterations in lung tissues following whole-lung CONV and FLASH irradiation. Plasma samples were collected from mice receiving whole-lung CONV irradiation (n = 5) and whole-lung FLASH irradiation (n = 5), followed by comparison with samples from the control group of healthy mice (also referred to as the healthy control group). These plasma samples were analyzed using isobaric tags for relative and absolute quantification (iTRAQ) -based proteomics, followed by the screening and identification of differentially expressed proteins using high-throughput bioinformatics. Moreover, protein-protein interaction (PPI) network analysis was conducted to identify hub genes using the STRING database and Cytoscape software. Results Whole-lung FLASH and CONV irradiation produced consistent tumor control, with the former significantly reducing RILI compared to the latter. A total of 609 proteins were identified through proteomic analysis. Among them, 89 differentially expressed proteins were detected in the whole-lung FLASH group. Gene Ontology (GO) enrichment analysis indicated that up-regulated genes were primarily associated with stress and inflammatory responses, whereas down-regulated genes were related to ATP metabolism and angiogenesis regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that up-regulated genes were predominantly enriched in unfolded protein response pathways, while down-regulated genes were mainly involved in metabolic pathways and oxidative phosphorylation. Integrated PPI analysis and subsequent validation via reverse transcription-polymerase chain reaction (RT-PCR) revealed four key genes. Conclusions Compared to the whole-lung CONV irradiation, whole-lung FLASH irradiation reduces the RILI of normal lung tissues while maintaining equivalent tumor control in metastatic lung cancer. Proteomic analysis of differentially expressed proteins in plasma after whole-lung FLASH and CONV irradiation provides valuable insights into the molecular mechanisms underlying the FLASH effect. |
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