[1]袁 牧,邢 伟,徐 祥.高原肺水肿新型生物标记物的研究[J].医学信息,2023,36(15):12-18.[doi:10.3969/j.issn.1006-1959.2023.15.003]
　YUAN Mu,XING Wei,XU Xiang.Research on Novel Biomarkers of High Altitude Pulmonary Edema[J].Journal of Medical Information,2023,36(15):12-18.[doi:10.3969/j.issn.1006-1959.2023.15.003]
点击复制

高原肺水肿新型生物标记物的研究()
分享到：

医学信息[ISSN:1006-1959/CN:61-1278/R]

卷:
36卷
期数:
2023年15期
页码:
12-18
栏目:
生物信息学
出版日期:
2023-08-01

文章信息/Info

Title:
Research on Novel Biomarkers of High Altitude Pulmonary Edema
文章编号:
1006-1959（2023）15-0012-07
作者:
袁 牧; 邢 伟; 徐 祥
（陆军军医大学大坪医院中心实验室，重庆 400042）
Author(s):
YUAN Mu; XING Wei; XU Xiang
(Central Laboratory of Daping Hospital,Army Medical University,Chongqing 400042,China)
关键词:
高原肺水肿; 发病机制; 诊断; 生物标志物; 枢纽基因; miRNA
Keywords:
High altitude pulmonary edema; Pathogenesis; Diagnosis; Biomarkers; Key hub genes; miRNA
分类号:
R563
DOI:
10.3969/j.issn.1006-1959.2023.15.003
文献标志码:
A
摘要:
目的 研究高原肺水肿的发生和早期进展潜在生物标志物，进一步为高海拔肺水肿的发病和早期进展机制提供理论基础。方法 从GEO数据库中提取出人类基因表达谱GSE52209，使用R软件在数据集中筛选急进入高原48~72 h内高原适应组和高原肺水肿组的差异表达基因（DEGs），通过GO和KEGG探究高原肺水肿的发生和早期进展机制，利用cytoscape软件的MCC算法鉴定枢纽基因，利用Lasso-Cox回归分析和ROC曲线分析预测和验证诊断标记物，利用R软件检测数据集枢纽基因的相对表达水平，利用networkanalyst和cytoscape软件鉴定与枢纽基因作用的miRNA和枢纽miRNA。结果 共鉴定出DEGs 216个，其中196个基因表达上调，20个基因表达下调；GO和KEGG分析结果显示，DEGs主要与代谢异常和氧化应激相关；共筛选出7个高原肺水肿诊断标记物（ARRB2、RPLP0、JAK2、ICAM1、ESPL1、RAD54L、SEC61A1），结合gene-miRNA网络，hsa-miR-335-5p、hsa-miR-16-5p、hsa-miR-149-5p和hsa-miR-615-3p可能是高原肺水肿发生和早期进展相关的枢纽miRNA。结论 ARRB2、RPLP0、JAK2、ICAM1、ESPL1、RAD54L、SEC61A1、hsa-miR-335-5p、hsa-miR-16-5p、hsa-miR-149-5p和hsa-miR-615-3p可能是高原肺水肿发病和早期进展的重要生物标记物，其中ARRB2、RPLP0、JAK2、ICAM1、ESPL1、RAD54L和SEC61A1可能是高原肺水肿的早期诊断标记物。
Abstract:
Objective To study the potential biomarkers of the occurrence and early progression of high altitude pulmonary edema, and to further provide a theoretical basis for the pathogenesis and early progression of high altitude pulmonary edema.Methods The human gene expression profile GSE52209 was extracted from the GEO database. R software was used to screen differentially expressed genes (DEGs) between the high-altitude adaptation group and the high-altitude pulmonary edema group within 48-72 h after rapid entry into the plateau in the data set. GO and KEGG were used to explore the mechanism of the occurrence and early progression of high-altitude pulmonary edema. The MCC algorithm of cytoscape software was used to identify hub genes. Lasso-Cox regression analysis and ROC curve analysis were used to predict and verify diagnostic markers. R software was used to detect the relative expression level of hub genes in the data set. Networkanalyst and cytoscape software were used to identify miRNAs and hub miRNAs that interact with hub genes.Results A total of 216 DEGs were identified, of which 196 genes were up-regulated and 20 genes were down-regulated. GO and KEGG analysis showed that DEGs were mainly related to metabolic abnormalities and oxidative stress. A total of 7 diagnostic markers of high altitude pulmonary edema(ARRB2, RPLP0, JAK2, ICAM1, ESPL1, RAD54L, SEC61A1) were screened out. Combined with gene-miRNA network, hsa-miR-335-5p, hsa-miR-16-5p, hsa-miR-149-5p and hsa-miR-615-3p may be hub miRNAs related to the occurrence and early progression of high altitude pulmonary edema.Conclusion ARRB2, RPLP0, JAK2, ICAM1, ESPL1, RAD54L, SEC61A1, hsa-miR-335-5p, hsa-miR-16-5p, hsa-miR-149-5p and hsa-miR-615-3p may be important biomarkers for the pathogenesis and early progression of high altitude pulmonary edema. ARRB2, RPLP0, JAK2, ICAM1, ESPL1, RAD54L and SEC61A1 may be early diagnostic markers for high altitude pulmonary edema.

参考文献/References:

[1]Si L,Wang H,Jiang Y,et al.MIR17HG polymorphisms contribute to high-altitude pulmonary edema susceptibility in the Chinese population[J].Sci Rep,2022,12(1):4346.[2]Gudbjartsson T,Sigurdsson E,Gottfredsson M,et al.High altitude illness and related diseases - a review[J].Laeknabladid,2019,105(11):499-507.[3]Zhou Q.Standardization of methods for early diagnosis and on-site treatment of high-altitude pulmonary edema[J].Pulm Med,2011,2011:190648.[4]Gordon-Rodriguez E,Quinn TP,Cunningham JP.Learning sparse log-ratios for high-throughput sequencing data[J].Bioinformatics,2021,38(1):157-163.[5]Mann M,Kumar C,Zeng WF,et al.Artificial intelligence for proteomics and biomarker discovery[J].Cell Syst,2021,12(8):759-770.[6]Zhong Y,Xu F,Wu J,et al.Application of Next Generation Sequencing in Laboratory Medicine[J].Ann Lab Med,2021,41(1):25-43.[7]Mellor A,Boos C,Holdsworth D,et al.Cardiac biomarkers at high altitude[J].High Alt Med Biol,2014,15(4):452-458.[8]Guo L,Tan G,Liu P,et al.Three plasma metabolite signatures for diagnosing high altitude pulmonary edema[J].Sci Rep,2015,5:15126.[9]Barker KR,Conroy AL,Hawkes M,et al.Biomarkers of hypoxia, endothelial and circulatory dysfunction among climbers in Nepal with AMS and HAPE: a prospective case-control study[J].J Travel Med,2016,23(3):taw005.[10]Petrache I,Natarajan V,Zhen L,et al.Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice[J].Nat Med,2005,11(5):491-498.[11]Oda Y,Kanahara N,Iyo M.Alterations of Dopamine D2 Receptors and Related Receptor-Interacting Proteins in Schizophrenia: The Pivotal Position of Dopamine Supersensitivity Psychosis in Treatment-Resistant Schizophrenia[J].Int J Mol Sci,2015,16(12):30144-30163.[12]Wang H,Deng QW,Peng AN,et al.β-arrestin2 functions as a key regulator in the sympathetic-triggered immunodepression after stroke[J].J Neuroinflammation,2018,15(1):102.[13]Cao F,Huang C,Cheng J,et al.β-arrestin-2 alleviates rheumatoid arthritis injury by suppressing NLRP3 inflammasome activation and NF- κB pathway in macrophages[J].Bioengineered,2022,13(1):38-47.[14]Javadi M,Richmond TD,Huang K,et al.CBL linker region and RING finger mutations lead to enhanced granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling via elevated levels of JAK2 and LYN[J].J Biol Chem,2013,288(27):19459-19470.[15]He S,Wang T,Shi C,et al.Network pharmacology-based approach to understand the effect and mechanism of Danshen against anemia[J].J Ethnopharmacol,2022,282:114615.[16]Xu S,Pan X,Mao L,et al.Phospho-Tyr705 of STAT3 is a therapeutic target for sepsis through regulating inflammation and coagulation[J].Cell Commun Signal,2020,18(1):104.[17]Xia Y,Hong Q,Gao Z,et al.Somatically acquired mutations in primary myelofibrosis: A case report and meta-analysis[J].Exp Ther Med,2021,21(3):193.[18]Zhou Q,Cheng KW,Gong J,et al.Apigenin and its methylglyoxal-adduct inhibit advanced glycation end products-induced oxidative stress and inflammation in endothelial cells[J].Biochem Pharmacol,2019,166:231-241.[19]Bui TM,Wiesolek HL,Sumagin R.ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis[J].J Leukoc Biol,2020,108(3):787-799.[20]Andersen CB,Runge Walther A,Pipó-Ollé E,et al.Falcarindiol Purified From Carrots Leads to Elevated Levels of Lipid Droplets and Upregulation of Peroxisome Proliferator-Activated Receptor-γ Gene Expression in Cellular Models[J].Front Pharmacol,2020,11:565524.[21]Nie Z,Pu T,Han Z,et al.Extra Spindle Pole Bodies-Like 1 Serves as a Prognostic Biomarker and Promotes Lung Adenocarcinoma Metastasis[J].Front Oncol,2022,12:930647.[22]Song R,Huang J,Yang C,et al.ESPL1 is Elevated in Hepatocellular Carcinoma and Predicts Prognosis[J].Int J Gen Med,2022,15:8381-8398.[23]Singh N,Sharma R,Bose S.Meta-analysis of transcriptomics data identifies potential biomarkers and their associated regulatory networks in gallbladder cancer[J].Gastroenterol Hepatol Bed Bench,2022,15(4):311-325.[24]Guan Q,Zhao P,Tian Y,et al.Identification of cancer risk assessment signature in patients with chronic obstructive pulmonary disease and exploration of the potential key genes[J].Ann Med,2022,54(1):2309-2320.[25]Wang Y,Zhou T,Chen H,et al.Rad54L promotes bladder cancer progression by regulating cell cycle and cell senescence[J].Med Oncol,2022,39(12):185.[26]De Luna N,Turon-Sans J,Cortes-Vicente E,et al.Downregulation of miR-335-5P in Amyotrophic Lateral Sclerosis Can Contribute to Neuronal Mitochondrial Dysfunction and Apoptosis[J].Sci Rep,2020,10(1):4308.[27]Xu SJ,Hu HT,Li HL,et al.The Role of miRNAs in Immune Cell Development, Immune Cell Activation, and Tumor Immunity: With a Focus on Macrophages and Natural Killer Cells[J].Cells,2019,8(10):1140.[28]Zhang Z,Chen L,Xu P,et al.Gene correlation network analysis to identify regulatory factors in sepsis[J].J Transl Med,2020,18(1):381.[29]Miao R,Dong XB,Gong JN,et al.Analysis of significant microRNA associated with chronic thromboembolic pulmonary hypertension[J].Natl Med J China,2018,98(18):1397-1402.[30]Yi E,Zhang J,Zheng M,et al.Long noncoding RNA IL6-AS1 is highly expressed in chronic obstructive pulmonary disease and is associated with interleukin 6 by targeting miR-149-5p and early B-cell factor 1[J].Clin Transl Med,2021,11(7):e479.[31]Yuan M,Hu X,Xing W,et al.B2M is a biomarker associated with immune infiltration in High altitude pulmonary edema[J].Comb Chem High Throughput Screen,2023 May 10.Epub ahead of print.[32]Swenson ER,B?覿rtsch P.High-altitude pulmonaryedema[J].Compr Physiol,2012,2(4):2753-2773.

相似文献/References:

[1]刘 璐,秦新月.阿尔茨海默病患者血尿酸水平变化的研究[J].医学信息,2018,31(02):96.[doi:10.3969/j.issn.1006-1959.2018.02.033]
　LIU Lu,QIN Xin-yue.Study on the Changes of Serum Uric Acid in Alzheimer 's Disease Patients[J].Journal of Medical Information,2018,31(15):96.[doi:10.3969/j.issn.1006-1959.2018.02.033]
[2]王玉霞.剖宫产术后子宫疤痕妊娠的临床诊治[J].医学信息,2018,31(10):48.[doi:10.3969/j.issn.1006-1959.2018.10.015]
　WANG Yu-xia.Clinical Diagnosis and Treatment of Uterine Scar Pregnancy after Cesarean Section[J].Journal of Medical Information,2018,31(15):48.[doi:10.3969/j.issn.1006-1959.2018.10.015]
[3]刘革铭,马洪俊,刘 毅,等.心力衰竭的机制及诊疗的研究[J].医学信息,2022,35(10):91.[doi:10.3969/j.issn.1006-1959.2022.10.022]
　LIU Ge-ming,MA Hong-jun,LIU Yi,et al.Mechanism, Diagnosis and Treatment of Heart Failure[J].Journal of Medical Information,2022,35(15):91.[doi:10.3969/j.issn.1006-1959.2022.10.022]
[4]只茂叶.重症急性胰腺炎的发病机制与内镜治疗研究[J].医学信息,2022,35(11):68.[doi:10.3969/j.issn.1006-1959.2022.11.019]
　ZHI Mao-ye.The Pathogenesis and Endoscopic Treatment of Severe Acute Pancreatitis[J].Journal of Medical Information,2022,35(15):68.[doi:10.3969/j.issn.1006-1959.2022.11.019]
[5]王煜婷.原发性痛经发病机制及口服药物治疗进展[J].医学信息,2018,31(13):56.[doi:10.3969/j.issn.1006-1959.2018.13.016]
　WANG Yu-ting.Research Progress in Pathogenesis and Oral Medication of Primary Dysmenorrhea[J].Journal of Medical Information,2018,31(15):56.[doi:10.3969/j.issn.1006-1959.2018.13.016]
[6]郑小鹏,辛 华.糖尿病肾病研究进展[J].医学信息,2018,31(16):26.[doi:10.3969/j.issn.1006-1959.2018.16.008]
　ZHENG Xiao-peng,XIN Hua.Progress in the Study of Diabetic Nephropathy[J].Journal of Medical Information,2018,31(15):26.[doi:10.3969/j.issn.1006-1959.2018.16.008]
[7]马宏境,刘 彬.慢性阻塞性肺疾病发病机制的研究[J].医学信息,2019,32(10):50.[doi:10.3969/j.issn.1006-1959.2019.10.018]
　MA Hong-jing,LIU Bin.Study on the Pathogenesis of Chronic Obstructive Pulmonary Disease[J].Journal of Medical Information,2019,32(15):50.[doi:10.3969/j.issn.1006-1959.2019.10.018]
[8]邵永康.维持性血液透析患者并发症的发病机制分析[J].医学信息,2019,32(17):35.[doi:10.3969/j.issn.1006-1959.2019.17.012]
　SHAO Yong-kang.Pathogenesis Analysis of Complications in Maintenance Hemodialysis Patients[J].Journal of Medical Information,2019,32(15):35.[doi:10.3969/j.issn.1006-1959.2019.17.012]
[9]齐尚忠,张 强.低位直肠癌前切除综合征的发病机制及防治研究[J].医学信息,2019,32(20):37.[doi:10.3969/j.issn.1006-1959.2019.20.011]
　QI Shang-zhong,ZHANG Qiang.Pathogenesis and Prevention of Low Rectal Cancer Anterior Resection Syndrome[J].Journal of Medical Information,2019,32(15):37.[doi:10.3969/j.issn.1006-1959.2019.20.011]
[10]杨 敏,汤云昭,倪长林.2型糖尿病患者心血管疾病的发病机制[J].医学信息,2020,33(06):56.[doi:10.3969/j.issn.1006-1959.2020.06.017]
　YANG Min,TANG Yun-zhao,NI Chang-lin.The Pathogenesis of Cardiovascular Disease in Patients with Type 2 Diabetes[J].Journal of Medical Information,2020,33(15):56.[doi:10.3969/j.issn.1006-1959.2020.06.017]

更新日期/Last Update: 1900-01-01