罗辉,王刘祥,Ron Leavitt,孙亚楠,宋帅,王晓辉,毛荣虎,马蕾杰,雷宏昌,葛红.基于基因表达综合数据库筛选调控急性T淋巴细胞白血病超高剂量率放疗敏感性的枢纽基因[J].中华放射医学与防护杂志,2022,42(10):738-744
基于基因表达综合数据库筛选调控急性T淋巴细胞白血病超高剂量率放疗敏感性的枢纽基因
Screening of Hub genes contributing to acute T lymphoblastic leukemia induced by ultra-high dose rate radiotherapy based on GEO database
投稿时间:2022-06-29  
DOI:10.3760/cma.j.cn112271-20220629-00273
中文关键词:  超高剂量率放疗  常规放疗  GEO数据库  放疗敏感性  枢纽基因
英文关键词:Ultra-high dose rate radiotherapy  Conventional radiotherapy  GEO database  Radiosensitivity  Hub genes
基金项目:国家自然科学基金(81773230);河南省科技攻关计划项目(212102310619)
作者单位E-mail
罗辉 郑州大学附属肿瘤医院肿瘤放疗科, 郑州 450008  
王刘祥 郑州大学医学科学院, 郑州 450001  
Ron Leavitt 洛桑大学附属医院放疗科, 洛桑 瑞士 1002  
孙亚楠 郑州大学附属肿瘤医院肿瘤放疗科, 郑州 450008  
宋帅 郑州大学附属肿瘤医院肿瘤放疗科, 郑州 450008  
王晓辉 郑州大学附属肿瘤医院肿瘤放疗科, 郑州 450008  
毛荣虎 郑州大学附属肿瘤医院肿瘤放疗科, 郑州 450008  
马蕾杰 郑州大学附属肿瘤医院肿瘤放疗科, 郑州 450008  
雷宏昌 郑州大学附属肿瘤医院肿瘤放疗科, 郑州 450008  
葛红 郑州大学附属肿瘤医院肿瘤放疗科, 郑州 450008 zlyygehong0199@zzu.edu.cn 
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中文摘要:
      目的 通过生物信息学方法对基因表达综合(GEO)数据库中超高剂量率(FLASH)放疗的数据进行分析,寻找参与调控急性T淋巴细胞白血病FLASH放疗敏感性的枢纽(Hub)基因。方法 从GEO数据库中下载和提取接受FLASH放疗恶性肿瘤基因表达谱芯片数据,采用R软件进行差异基因的筛选,并对这些基因进行生物学功能、信号传导通路等分析。通过STRING在线软件分析差异基因的蛋白质相互作用(PPI) 网络,Cytoscape插件筛选Hub基因。最后,应用肿瘤基因组图谱(TCGA)和GTEx数据库验证Hub基因在急性T淋巴细胞白血病中的表达情况。结果 自GEO数据库中获得GSE100718芯片数据,共有12 800个基因与急性T淋巴细胞白血病放疗敏感性相关。选择表达量显著改变的61个基因进行进一步分析,这些基因参与代谢、应激反应、免疫应答等生物学过程。主要涉及氧化磷酸化、未折叠蛋白应答、脂质代谢等信号转导通路。通过PPI分析筛选出的Hub基因及后续验证表明HSPA5及SCD参与调控FLASH放疗敏感性,且在合并TRD/LMO2融合基因的急性T淋巴细胞白血病中显著高表达。结论 通过生物信息学分析可以有效筛选出调控FLASH放疗敏感性的Hub基因,基因表达谱可用于指导肿瘤患者分层以实现精准放疗。
英文摘要:
      Objective To analyze the data of ultra-high dose rate (FLASH) radiotherapy in GEO (Gene Expression Omnibus) database by bioinformatics method, in order to find the hub genes involved in flash radiotherapy induced acute T-lymphoblastic leukemia.Methods The gene expression profiles of malignant tumors receiving FLASH radiotherapy were downloaded from GEO database. The R software was used to screen the differential expressed genes (DEGs) and analyze their biological functions and signal pathways. The protein-protein interaction (PPI) network of DEGs was analyzed by online tool of STRING, and Hub genes were screened by Cytoscape plug-in. The expressions of screened Hub genes in acute T lymphoblastic leukemia were identified with TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) database.Results Based on the analysis of GSE100718 microarray dataset of GEO database, a total of 12 800 genes were found to be associated with radiosensitivity of acute T lymphoblastic leukemia, of which 61 significantly altered DEGs were selected for further analysis. It was found that these genes were involved in the biological processes of metabolism, stress response, and immune response through the pathways of oxidative phosphorylation, unfolded protein response, fatty acid metabolism, and so on. PPI analysis indicated that HSPA5 and SCD belonged to the Hub genes involved in the regulation of FLASH radiosensitivity, and they were significantly highly expressed in acute T lymphoblastic leukemia combined with TRD/LMO2-fusion gene.Conclusions Through bioinformatics analysis, the Hub genes involved in regulating the sensitivity of FLASH radiotherapy and conventional radiotherapy can be effectively screened, and thus the gene expression profiles can be used to guide the stratification of cancer patients to achieve a precise radiotherapy.
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