[1]袁 牧,邢 伟,徐 祥.脓毒症患者发生急性肺损伤的机制和生物标记物研究[J].医学信息,2023,36(16):1-7.[doi:10.3969/j.issn.1006-1959.2023.16.001]
 YUAN Mu,XING Wei,XU Xiang.Study on the Mechanism and Biomarkers of Acute Lung Injury in Patients with Sepsis[J].Journal of Medical Information,2023,36(16):1-7.[doi:10.3969/j.issn.1006-1959.2023.16.001]
点击复制

脓毒症患者发生急性肺损伤的机制和生物标记物研究()
分享到:

医学信息[ISSN:1006-1959/CN:61-1278/R]

卷:
36卷
期数:
2023年16期
页码:
1-7
栏目:
生物信息学
出版日期:
2023-08-15

文章信息/Info

Title:
Study on the Mechanism and Biomarkers of Acute Lung Injury in Patients with Sepsis
文章编号:
1006-1959(2023)16-0001-07
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 MuXING WeiXU Xiang
(Central Laboratory of Daping Hospital,Army Medical University,Chongqing 400042,China)
关键词:
脓毒症急性肺损伤生物标记物CDKN1AmicroRNA-335-5p
Keywords:
SepsisAcute lung injuryBiomarkerCDKN1AmicroRNA-335-5p
分类号:
R563
DOI:
10.3969/j.issn.1006-1959.2023.16.001
文献标志码:
A
摘要:
目的 探索脓毒症患者发生急性肺损伤的发病机制和生物标记物。方法 利用R语言在GEO数据库中筛选脓毒症和脓毒症合并急性肺损伤患者两组转录组数据集的差异基因,利用String数据库构建差异基因蛋白-蛋白相互作用网络,利用Cytoscape软件鉴定枢纽基因,利用R语言分析枢纽基因在两组数据集mRNA的相对表达和表达相关性;利用miRTarBase数据库和NetworkAnalys网站构建miRNA-gene网络,筛选与枢纽基因作用的miRNA,利用CIBERSORTx网站对两组数据集进行免疫细胞浸润评估,利用CTD数据库搜索与脓毒症合并急性肺损伤相关的生物标记物作用的分子化合物,以预测脓毒症合并急性肺损伤的治疗药物。结果 共鉴定出差异基因12个,其中3个表达上调,9个表达下调;脓毒症患者发生急性肺损伤机制与细胞周期缩短、细胞凋亡增加、细胞铁死亡增加相关;枢纽miRNA miR-335-5p和枢纽基因CDKN1A可能是脓毒症合并急性肺损伤与发病机制相关的重要生物标记物和靶向治疗标记物,共有687种分子化合物与CDKN1A作用,发挥上调其表达的作用。结论 miR-335-5p和CDKN1A可能是脓毒症合并急性肺损伤潜在的与发病机制相关的重要生物标记物。
Abstract:
Objective To explore the pathogenesis and biomarkers of acute lung injury in patients with sepsis.Methods The GEO database was used to screen the differential genes in the transcriptome datasets of sepsis and sepsis with acute lung injury using R language; the differential gene protein-protein interaction network was constructed using the String database; the key genes were identified using Cytoscape software; R language was used to analyze the relative expression and expression correlation of hub gene mRNA in the two data sets; the miRNA-gene network was constructed using the miRTarBase database and the NetworkAnalys website to screen the miRNAs that interact with the hub genes. The CIBERSORTx website was used to evaluate the immune cell infiltration of the two sets of data sets. The CTD database was used to search for molecular compounds related to biomarkers associated with sepsis complicated with acute lung injury to predict the therapeutic drugs for sepsis complicated with acute lung injury.Results A total of 12 differential genes were identified, of which 3 genes were up-regulated and 9 genes were down-regulated; the mechanism of acute lung injury in patients with sepsis was related to shortened cell cycle, increased apoptosis, and increased ferroptosis; the hub miRNA miR-335-5p and the hub gene CDKN1A might be important biomarkers and targeted therapeutic markers related to the pathogenesis of sepsis complicated with acute lung injury. A total of 687 molecular compounds interacted with CDKN1A and played a role in up-regulating its expression.Conclusion miR-335-5p and CDKN1A may be potentially important biomarkers related to the pathogenesis of sepsis patients with acute lung injury.

参考文献/References:

[1]Rudd KE,Johnson SC,Agesa KM,et al.Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study[J].Lancet,2020,395(10219):200-211.[2]Srzic I,Nesek AV,Tunjic PD.Sepsis Definition: What’s New ?In The Treatment Guidelines[J].Acta Clin Croat,2022,61(Suppl 1):67-72.[3]Wang Z,Rui T,Yang M,et al.Alveolar macrophages from septic mice promote polymorphonuclear leukocyte transendothelial migration via an endothelial cell Src kinase/NADPH oxidase pathway[J].J Immunol,2008,181(12):8735-8744.[4]Kumar V.Pulmonary Innate Immune Response Determines the Outcome of Inflammation During Pneumonia and Sepsis-Associated Acute Lung Injury[J].Front Immunol,2020,11:1722.[5]Howrylak JA,Dolinay T,Lucht L,et al.Discovery of the gene signature for acute lung injury in patients with sepsis[J].Physiol Genomics,2009,37(2):133-139.[6]Wang YM,Qi X,Gong FC,et al.Protective and predictive role of Mucin1 in sepsis-induced ALI/ARDS[J].Int Immunopharmacol,2020,83:106438.[7]Rego SM,Snyder MP.High Throughput Sequencing and Assessing Disease Risk[J].Cold Spring Harb Perspect Med,2019,9(1):a026849.[8]Oliver GR,Hart SN,Klee EW.Bioinformatics for clinical next generation sequencing[J].Clin Chem,2015,61(1):124-135.[9]Ho P,Clark IM,Le LTT.MicroRNA-Based Diagnosis and Therapy[J].Int J Mol Sci,2022,23(13):7167.[10]Bone RC,Balk RA,Cerra FB,et al.definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis[J].Crit Care Med,1992,20(6):864-874.[11]Bernard GR,Artigas A,Brigham KL,et al.The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination[J].Am J Respir Crit Care Med,1994,149(3 Pt 1):818-824.[12]Szklarczyk D,Gable AL,Nastou KC,et al.The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets[J].Nucleic Acids Res,2021,49(D1):D605-D612.[13]Pripp AH.Pearson’s or Spearman’s correlation coefficients[J].Tidsskr Nor Laegeforen,2018,138(8).[14]Huang HY,Lin YC,Cui S,et al.miRTarBase update 2022: an informative resource for experimentally validated miRNA-target interactions[J].Nucleic Acids Res,2022,50(D1):D222-D230.[15]Tibshirani R.The lasso method for variable selection in the Cox model[J].Stat Med,1997,16(4):385-395.[16]Chen L,Heikkinen L,Wang C,et al.Trends in the development of miRNA bioinformatics tools[J].Brief Bioinform,2019,20(5):1836-1852.[17]Li S,Han F,Qi N,et al.Determination of a six-gene prognostic model for cervical cancer based on WGCNA combined with LASSO and Cox-PH analysis[J].World J Surg Oncol,2021,19(1):277.[18]Fan E,Fan J.Regulation of alveolar macrophage death in acute lung inflammation[J].Respir Res,2018,19(1):50.[19]Guerrero-Fonseca IM,García-Ponce A,Vadillo E,et al.HS1 deficiency protects against sepsis by attenuating neutrophil-inflicted lung damage[J].Eur J Cell Biol,2022,101(2):151214.[20]Abbas T,Dutta A.p21 in cancer: intricate networks and multiple activities[J].Nat Rev Cancer,2009,9(6):400-414.[21]Kreis NN,Louwen F,Yuan J.Less understood issues: p21(Cip1) in mitosis and its therapeutic potential[J].Oncogene,2015,34(14):1758-1767.[22]Romanov VS,Rudolph KL.p21 shapes cancer evolution[J].Nat Cell Biol,2016,18(7):722-724.[23]Waga S,Hannon GJ,Beach D,et al.The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA[J].Nature,1994,369(6481):574-578.[24]Yang D,Yan Y,Hu F,et al.CYP1B1, VEGFA, BCL2, and CDKN1A Affect the Development of Chronic Obstructive Pulmonary Disease[J].Int J Chron Obstruct Pulmon Dis,2020,15:167-175.[25]Yang J,Zhang MY,Du YM,et al.Identification and Validation of CDKN1A and HDAC1 as Senescence-Related Hub Genes in Chronic Obstructive Pulmonary Disease[J].Int J Chron Obstruct Pulmon Dis,2022,17:1811-1825.[26]Fan J,Chen M,Cao S,et al.Identification of a ferroptosis-related gene pair biomarker with immune infiltration landscapes in ischemic stroke: a bioinformatics-based comprehensive study[J].BMC Genomics,2022,23(1):59.[27]Tarangelo A,Magtanong L,Bieging-Rolett KT,et al.p53 Suppresses Metabolic Stress-Induced Ferroptosis in Cancer Cells[J].Cell Rep,2018,22(3):569-575.[28]Chen R,Cao J,Jiang W,et al.Upregulated Expression of CYBRD1 Predicts Poor Prognosis of Patients with Ovarian Cancer[J].J Oncol,2021,2021:7548406.[29]Gao XL,Li JQ,Dong YT,et al.Upregulation of microRNA-335-5p reduces inflammatory responses by inhibiting FASN through the activation of AMPK/ULK1 signaling pathway in a septic mouse model[J].Cytokine,2018,110:466-478.[30]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.[31]Liang Q,He J,Yang Q,et al.MicroRNA-335-5p alleviates inflammatory response, airway fibrosis, and autophagy in childhood asthma through targeted regulation of autophagy related 5[J].Bioengineered,2022,13(1):1791-1801.[32]Sun D,Ma T,Zhang Y,et al.Overexpressed miR-335-5p reduces atherosclerotic vulnerable plaque formation in acute coronary syndrome[J].J Clin Lab Anal,2021,35(2):e23608.[33]Lu W,Ma YY,Shao QQ,et al.ROS/p53/miR-335-5p/Sp1 axis modulates the migration and epithelial to mesenchymal transition of JEG-3 cells[J].Mol Med Rep,2020,21(3):1208-1216.[34]Gu X,Yao X,Liu D.Up-regulation of microRNA-335-5p reduces inflammation via negative regulation of the TPX2-mediated AKT/GSK3β signaling pathway in a chronic rhinosinusitis mouse model[J].Cell Signal,2020,70:109596.[35]Kang Z,Zhu J,Sun N,et al.COL11A1 promotes esophageal squamous cell carcinoma proliferation and metastasis and is inversely regulated by miR-335-5p[J].Ann Transl Med,2021,9(20):1577.[36]Li J,Feng Z,Chen L,et al.MicroRNA-335-5p inhibits osteoblast apoptosis induced by high glucose[J].Mol Med Rep,2016,13(5):4108-4112.

相似文献/References:

[1]杨 雍,吕汝琦,刘 丹.早期无创正压通气对重症急性胰腺炎合并肺损伤的保护作用机制[J].医学信息,2019,32(03):55.[doi:10.3969/j.issn.1006-1959.2019.03.018]
 YANG Yong,LV Ru-qi,LIU Dan.Protective Mechanism of Early Noninvasive Positive Pressure Ventilation on Severe Acute Pancreatitis Complicated with Lung Injury[J].Journal of Medical Information,2019,32(16):55.[doi:10.3969/j.issn.1006-1959.2019.03.018]
[2]申 贵,彭 翔,秦光梅.抗感染督导治疗对脓毒症患者预后影响的研究[J].医学信息,2019,32(01):82.[doi:10.3969/j.issn.1006-1959.2019.01.026]
 SHEN Gui,PENG Xiang,QIN Guang-mei.Study on the Effect of Anti-infective Supervision on the Prognosis of Patients with Sepsis[J].Journal of Medical Information,2019,32(16):82.[doi:10.3969/j.issn.1006-1959.2019.01.026]
[3]张恺悦,陈幼琼.乌司他丁联合血必净对烧伤后脓毒症患者凝血功能及全身炎性反应的影响研究[J].医学信息,2019,32(04):138.[doi:10.3969/j.issn.1006-1959.2019.04.044]
 ZHANG Kai-yue,CHEN You-qiong.Effect of Ulinastatin Combined with Xuebijing on Coagulation Function and Systemic Inflammatory Response in Patients with Sepsis after Burn[J].Journal of Medical Information,2019,32(16):138.[doi:10.3969/j.issn.1006-1959.2019.04.044]
[4]张文旭,徐 绸.红细胞宽度对脓毒症患者病情诊断及预后评估的价值[J].医学信息,2022,35(14):71.[doi:10.3969/j.issn.1006-1959.2022.14.015]
 ZHANG Wen-xu,XU Chou.The Value of Red-blood-cell Distribution Width in the Diagnosis and Prognosis of Patients with Sepsis[J].Journal of Medical Information,2022,35(16):71.[doi:10.3969/j.issn.1006-1959.2022.14.015]
[5]朱思哲,叶成林.基于生物信息学分析构建免疫相关基因脓毒症预后模型[J].医学信息,2022,35(15):1.[doi:10.3969/j.issn.1006-1959.2022.15.001]
 ZHU Si-zhe,YE Cheng-lin.Identification of Immune-related Gene Prognostic Model for Sepsis Based on Bioinformatics Analysis[J].Journal of Medical Information,2022,35(16):1.[doi:10.3969/j.issn.1006-1959.2022.15.001]
[6]杨勋能.参苓白术散对脓毒症患者肠道功能的影响[J].医学信息,2019,32(16):146.[doi:10.3969/j.issn.1006-1959.2019.16.049]
 YANG Xun-neng.Effect of Shenling Baizhu Powder on Intestinal Function in Patients with Sepsis[J].Journal of Medical Information,2019,32(16):146.[doi:10.3969/j.issn.1006-1959.2019.16.049]
[7]杜金洁,胡 鹏.ESKAPE病原菌感染引起脓毒症的研究[J].医学信息,2019,32(21):33.[doi:10.3969/j.issn.1006-1959.2019.21.012]
 DU Jin-jie,HU Peng.Study on Sepsis Caused by ESKAPE Pathogen Infection[J].Journal of Medical Information,2019,32(16):33.[doi:10.3969/j.issn.1006-1959.2019.21.012]
[8]刘安平,段海真,汪 松.抗菌肽LL-37的生物学活性及其作用[J].医学信息,2019,32(24):13.[doi:10.3969/j.issn.1006-1959.2019.24.005]
 LIU An-ping,DUAN Hai-zhen,WANG Song.Biological Activity and Effect of Antibacterial Peptide LL-37[J].Journal of Medical Information,2019,32(16):13.[doi:10.3969/j.issn.1006-1959.2019.24.005]
[9]陈冀远.右美托咪啶对脓毒症急性肾损伤患者肾功能及血管紧张素Ⅱ表达的影响[J].医学信息,2020,33(01):142.[doi:10.3969/j.issn.1006-1959.2020.01.045]
 CHEN Ji-yuan.Effect of Dexmedetomidine on Renal Function and Angiotensin Ⅱ Expression in Patients with Acute Renal Injury in Sepsis[J].Journal of Medical Information,2020,33(16):142.[doi:10.3969/j.issn.1006-1959.2020.01.045]
[10]赵振宇.miR-33表达与炎症反应的关系[J].医学信息,2020,33(02):73.[doi:10.3969/j.issn.1006-1959.2020.02.020]
 ZHAO Zhen-yu.Relationship Between miR-33 Expression and Inflammatory Response[J].Journal of Medical Information,2020,33(16):73.[doi:10.3969/j.issn.1006-1959.2020.02.020]
[11]温占兵.血管生成素-1水平变化预测脓毒症急性肺损伤的价值[J].医学信息,2018,31(13):95.[doi:10.3969/j.issn.1006-1959.2018.13.027]
 WEN Zhan-bing.The Value of Angiopoietin-1 Level Change in Predicting Acute Lung Injury in Sepsis[J].Journal of Medical Information,2018,31(16):95.[doi:10.3969/j.issn.1006-1959.2018.13.027]

更新日期/Last Update: 1900-01-01