[1]向杰 刘明鑫 张伟 黄从新.基于生物信息学分析探究肺动脉高压关键基因和通路[J].心血管病学进展,2020,(4):428-433.[doi:10.16806/j.cnki.issn.1004-3934.2020.04.024]
　Xiang JieLiu MingxinZhang WeiHuang Congxin.Bioinformatics Analysis of Key Genes and Pathways in Pulmonary Arterial Hypertension[J].Advances in Cardiovascular Diseases,2020,(4):428-433.[doi:10.16806/j.cnki.issn.1004-3934.2020.04.024]
点击复制

基于生物信息学分析探究肺动脉高压关键基因和通路()
分享到：

《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2020年4期
页码:
428-433
栏目:
论著
出版日期:
2020-04-25

文章信息/Info

Title:
Bioinformatics Analysis of Key Genes and Pathways in Pulmonary Arterial Hypertension
作者:
向杰 刘明鑫 张伟 黄从新
(武汉大学人民医院心内科,湖北 武汉 430060)
Author(s):
Xiang JieLiu MingxinZhang WeiHuang Congxin
(Department of CardiologyRenmin Hospital of Wuhan UniversityWuhan 430060 HubeiChina)
关键词:
肺动脉高压; 生物信息学分析; 差异表达基因; 基因芯片
Keywords:
Pulmonary arterial hypertension;  Bioinformatics analysis;  Differentially expressed genes;  Gene chip
DOI:
10.16806/j.cnki.issn.1004-3934.2020.04.024
摘要:
目的 通过生物信息学方法寻找肺动脉高压中差异表达的基因，为肺动脉高压的预防和早期诊断及治疗提供新思路。方法 从公共基因数据库（GEO）中下载基因芯片数据集GSE113439，使用在线分析工具GEO2R筛选出肺动脉高压肺组织和正常肺组织的差异表达基因。利用在线数据库DAVID和STRING分别进行功能、通路富集分析和蛋白互作分析，使用Cytoscape软件来筛选蛋白相互作用网络中的核心网络基因及显著相互作用模块。结果 共筛选出559个差异基因，其中87个为上调基因，472个为下调基因（调整后P<0.05，|log2FC|>1）。对差异基因进行GO和KEGG富集分析，GO富集分析（P<0.05）结果提示：（1）生物过程：差异表达基因显著富集于DNA双解、DNA修复、有丝分裂等；（2）细胞单位：差异表达基因显著富集于核质、膜、核仁、细胞质、中心体、核、核斑点、染色体、高尔基体等；（3）分子功能：差异表达基因显著富集于聚（A）RNA结合、ATP结合、蛋白质结合、解旋酶活性、微管结合、ATP依赖性DNA解旋酶活性等。KEGG富集分析结果提示差异表达基因显著富集于真核生物的核糖体生物发生、RNA转运、类风湿性关节炎、RNA降解、血管平滑肌收缩、疟疾、癌症中的蛋白多糖等（P<0.05）。STRING分析发现了蛋白质网络互作图中的10个关键基因，分别为CDK1、CDC5L、KIF11、SMC2、CENPE、TOP2A、NCAPG、CENPF、SMC4、SKIV2L2。结论 细胞增殖与凋亡等生物学过程和肺血管平滑肌等通路可能在肺动脉高压发生发展过程中起着重要的作用，采用生物信息学方法筛选可能的核心靶点有利于从基因层面上了解疾病的发生机制，为肺动脉高压发生机制的进一步研究提供方向。
Abstract:
To find the differentially expressed genes in pulmonary arterial hypertension by bioinformatics method, and to provide new ideas for the prevention and early diagnosis and treatment of pulmonary hypertension. Methods The gene chip dataset GSE113439 was downloaded from the Gene Expression Omnibus (GEO), and differentially expressed genes in pulmonary arterial hypertension lung tissue and normal lung tissue were screened using the online analysis tool GEO2R. We used the online databases DAVID and STRING for functional, pathway enrichment analysis and protein interaction analysis, and Cytoscape software was also used to screen core network genes and significant interaction modules in protein interaction networks.Results A total of 559 differential genes were screened, of which 87 were up-regulated and 472 were down-regulated (P<0.05 after adjustment, |log2FC|>1).GO and KEGG enrichment analysis of differential genes, GO enrichment analysis (P<0.05) showed that:(1)Biological process: differentially expressed genes are significantly enriched in DNA duplex unwinding, DNA repair, mitotic nuclear division, etc; (2)Cellar locution：differentially expressed genes are significantly enriched in nucleoplasm, membrane, nucleolus, cytoplasm, centrosome, nucleus, nuclear speck, Chromosome, Golgi apparatus, etc;(3)Molecular functions: differentially expressed genes are significantly enriched in poly(A)RNA binding, ATP binding, protein binding, helicase activity, microtubule binding, ATP-dependent DNA helicase activity, etc. KEGG enrichment analysis suggested that differentially expressed genes were significantly enriched in Ribosome biogenesis in eukaryotes, RNA transport, rheumatoid arthritis, RNA degradation, vascular smooth muscle contraction, malaria, Proteoglycans in cancer and so on (P<0.05). STRING analysis found 10 key genes in the protein network interaction map, namely CDK1, CDC5L, KIF11, SMC2, CENPE, TOP2A, NCAPG, CENPF, SMC4, SKIV2L2. Conclusion Biological processes such as cell proliferation and apoptosis and pulmonary vascular smooth muscle may play an important role in the development of pulmonary hypertension. The use of bioinformatics methods to screen possible core targets is beneficial to understand the mechanism of disease at the genetic level and provide direction for further research on the mechanism of pulmonary arterial hypertension.

参考文献/References:


[1] Peacock AJ,Murphy NF,McMurray JJ,et al. An epidemiological study of pulmonary arterial hypertension[J]. Eur Respir J,2007,30(1):104-109.

[2] Gaine SP,Rubin LJ. Primary pulmonary hypertension[J]. Lancet,1998,352(9129):719-725.

[3] Tuder RM,Archer SL,Dorfmuller P,et al. Relevant issues in the pathology and pathobiology of pulmonary hypertension[J]. J Am Coll Cardiol,2013,62(25 Suppl):D4-D12.

[4] Southgate L,Machado RD,Graf S,et al. Molecular genetic framework underlying pulmonary arterial hypertension[J]. Nat Rev Cardiol,2020,17(2):85-95.

[5] Hoeper MM,Ghofrani HA,Grunig E,et al. Pulmonary hypertension[J]. Dtsch Arztebl Int,2017,114(5):73-84.

[6] 石文海,黄玮,蔡琳. 肺动脉高压新型治疗方式展望[J]. 心血管病学进展,2017(1):57-59.

[7] Guo Y,Bao Y,Ma M,et al. Identification of key candidate genes and pathways in colorectal cancer by integrated bioinformatical analysis[J]. Int J Mol Sci,2017,18(4):722.

[8] Hoeper MM,Humbert M,Souza R,et al. A global view of pulmonary hypertension[J]. Lancet Respir Med,2016,4(4):306-322.

[9] Rosenkranz S,Gibbs JS,Wachter R,et al. Left ventricular heart failure and pulmonary hypertension[J]. Eur Heart J,2016,37(12):942-954.

[10] Hoeper MM,Huscher D,Ghofrani HA,et al. Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry[J]. Int J Cardiol,2013,168(2):871-880.

[11] Ke R,Wu Y,Wang G,et al. Research progress in the correlation between insulin resistance and pulmonary arterial hypertension[J]. Nan Fang Yi Ke Da Xue Xue Bao,2015,35(2):301-305.

[12] Chin KM,Rubin LJ. Pulmonary arterial hypertension[J]. J Am Coll Cardiol,2008,51(16):1527-1538.

[13] Greer-Short A,Musa H,Alsina KM,et al. Calmodulin kinase Ⅱ regulates atrial myocyte late sodium current ,calcium handling and atrial arrhythmia[J]. Heart Rhythm,2019,S1547-5271(19)30922-1.

[14] de Mendonca L,Felix NS,Blanco NG,et al. Mesenchymal stromal cell therapy reduces lung inflammation and vascular remodeling and improves hemodynamics in experimental pulmonary arterial hypertension[J]. Stem Cell Res Ther,2017,8(1):220.

[15] Tuder RM,Abman SH,Braun T,et al. Development and pathology of pulmonary hypertension[J]. J Am Coll Cardiol,2009,54(1 Suppl):S3-S9.

[16] Schermuly RT,Ghofrani HA,Wilkins MR,et al. Mechanisms of disease: pulmonary arterial hypertension[J]. Nat Rev Cardiol,2011,8(8):443-455.

[17] Machado RD,Aldred MA,James V,et al. Mutations of the TGF-beta type Ⅱ receptor BMPR2 in pulmonary arterial hypertension[J]. Hum Mutat,2006,27(2):121-132.

[18] Harrison RE,Berger R,Haworth SG,et al. Transforming growth factor-beta receptor mutations and pulmonary arterial hypertension in childhood[J]. Circulation,2005,111(4):435-441.

[19] Austin ED,Ma L,LeDuc C,et al. Whole exome sequencing to identify a novel gene (caveolin-1) associated with human pulmonary arterial hypertension[J]. Circ Cardiovasc Genet,2012,5(3):336-343.

[20] Eddahibi S,Humbert M,Fadel E,et al. Serotonin transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension[J]. J Clin Invest,2001,108(8):1141-1150.

[21] Ma L,Chung WK. The genetic basis of pulmonary arterial hypertension[J]. Hum Genet,2014,133(5):471-479.

相似文献/References:

[1]孟晓冬,单福祥,综述,等.肺动脉高压治疗进展[J].心血管病学进展,2016,(3):319.[doi:10.16806/j.cnki.issn.1004-3934.2016.03.028]
　MENG Xiaodong,SHAN Fuxiang,WANG Yanhui.Advances in Research of Pulmonary Hypertension[J].Advances in Cardiovascular Diseases,2016,(4):319.[doi:10.16806/j.cnki.issn.1004-3934.2016.03.028]
[2]张艺韬,综述,曾伟杰,等.左心疾病相关肺动脉高压流行病学[J].心血管病学进展,2016,(4):333.[doi:10.16806/j.cnki.issn.1004-3934.2016.04.002]
　ZHANG Yitao,ZENG Weijie,CHENG Kanglin.Epidemiology of Pulmonary Hypertension due to Left Heart Disease[J].Advances in Cardiovascular Diseases,2016,(4):333.[doi:10.16806/j.cnki.issn.1004-3934.2016.04.002]
[3]汪汉,刘英杰,王燕凤.长链非编码RNA与肺动脉高压[J].心血管病学进展,2019,(6):898.[doi:10.16806/j.cnki.issn.1004-3934.2019.06.015]
　WANG Han,LIU Yingjie,WANG Yanfeng.Long Non-coding RNA in Pulmonary Arterial Hypertension[J].Advances in Cardiovascular Diseases,2019,(4):898.[doi:10.16806/j.cnki.issn.1004-3934.2019.06.015]
[4]汪汉 邓祁 刘英杰.系统性红斑狼疮相关肺动脉高压的诊断、治疗及预后[J].心血管病学进展,2019,(8):1142.[doi:10.16806/j.cnki.issn.1004-3934.2019.08.018]
　WANG Han,DENG Qi,LIU Yingjie.Diagnosis,Treatment and Prognosis of Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus[J].Advances in Cardiovascular Diseases,2019,(4):1142.[doi:10.16806/j.cnki.issn.1004-3934.2019.08.018]
[5]段宇 贾静 步睿 李涛 韦宏.急性伊洛前列素吸入对肺动脉高压患者右心室功能的影响[J].心血管病学进展,2019,(9):1319.[doi:10.16806/j.cnki.issn.1004-3934.2019.09.034]
　DUAN Yu,JIA Jing,BU Rui,et al.The Effect of Acute Iloprost Inhalation on Right Ventricular Function in Pulmonary Arterial Hypertension[J].Advances in Cardiovascular Diseases,2019,(4):1319.[doi:10.16806/j.cnki.issn.1004-3934.2019.09.034]
[6]查玉杰 何庆.肺动脉高压发生发展中的相关因子[J].心血管病学进展,2020,(2):192.[doi:10.16806/j.cnki.issn.1004-3934.2020.02.024]
　ZHA YujieHE Qing.The Relevant Factors in the Development of Pulmonary Hypertension[J].Advances in Cardiovascular Diseases,2020,(4):192.[doi:10.16806/j.cnki.issn.1004-3934.2020.02.024]
[7]朱珊英,朱国斌.肺动脉高压发病机制新进展[J].心血管病学进展,2020,(3):292.[doi:10.16806/j.cnki.issn.1004-3934.2020.03.019]
　ZHU Shanying,ZHU Guobin.Pathogenesis of Pulmonary Hypertension[J].Advances in Cardiovascular Diseases,2020,(4):292.[doi:10.16806/j.cnki.issn.1004-3934.2020.03.019]
[8]韩柯,孟祥光,赵育洁.趋化因子及其受体在肺动脉高压中的研究进展[J].心血管病学进展,2020,(3):296.[doi:10.16806/j.cnki.issn.1004-3934.2020.03.020]
　HAN Ke,MENG Xiangguang,ZHAO Yujie.Chemokines and Their Receptors in Pulmonary Arterial Hypertension[J].Advances in Cardiovascular Diseases,2020,(4):296.[doi:10.16806/j.cnki.issn.1004-3934.2020.03.020]
[9]刘超 曲杰 王明娟 徐倩 范彦芳 周晓慧 单伟超.肺动脉高压对扩张型心肌病预后的影响[J].心血管病学进展,2020,(4):424.[doi:10.16806/j.cnki.issn.1004-3934.2020.04.023]
　LIU ChaoQU JieWANG MingjuanXU QianFAN YanfangZHOU XiaohuiSAN Weichao.The Effect of Pulmonary Hypertension on the Prognosis of Dilated Cardiomyopathy[J].Advances in Cardiovascular Diseases,2020,(4):424.[doi:10.16806/j.cnki.issn.1004-3934.2020.04.023]
[10]刘雪鸢 徐燕萍 殷跃辉.交感神经去除术在肺动脉高压治疗中的研究进展[J].心血管病学进展,2020,(5):480.[doi:10.16806/j.cnki.issn.1004-3934.2020.05.010]
　LIU Xueyuan,XU Yanping,YIN Yuehui.Sympathetic Denervation in Treatment of Pulmonary Hypertension[J].Advances in Cardiovascular Diseases,2020,(4):480.[doi:10.16806/j.cnki.issn.1004-3934.2020.05.010]

备注/Memo

备注/Memo:
通讯作者：黄从新，E-mail：Huangcongxin@VIP.163.com
收稿日期：2019-10-19
更新日期/Last Update: 2020-07-29