基于KEGG通路和基因网络对慢性萎缩性胃炎靶点基因的筛选
|
摘要
目的运用DAVID数据库得到通路和基因的相关信息,分析出重要基因的功能和分布,筛选出与慢性萎缩性胃炎(CAG)相关的靶点基因,促进对CAG发病机制的研究以及新药的开发。方法 2018年6月以"chronic atrophic gastritis"为关键词在NCBI数据库中检索CAG的相关基因,将得到的基因数据导入DAVID数据库,得到基因富集的通路数据。15个非冗余基因富集在20条KEGG通路上进行了分析,将15个基因输入String数据库做相互作用的网络图,将富集在通路上的关键基因也做网络图,并且将这两个网络图进行比较。结果在两张网络图中,FASLG、FAS、ICAM1、IL1B、AKT1、STAT3、TGFβ1、IL4R、IL11、IL23A是位于关系度排名靠前的基因。结论STAT3、ICAM1、IL1B、TGFβ1和AKT1五个基因与CAG相关,需要进一步深入研究,通过分析与疾病相关基因的所在通路和基因之间互作的网络图,有利于了解疾病的发病机制,并为新药研发提供可靠的靶点。
Objective By means of DAVID database, the information related to pathway and gene was obtained, the function and distribution of important gene was analyzed, the target gene related to chronic atrophic gastritis(CAG) was screened, so as to promote the research on CAG pathogenesis and the development of new drug. Methods By taking"chronic atrophic gastritis" as key words, the gene related to CAG was retrieved in NCBI database in June 2018 and the obtained gene data was imported into DAVID database, then the pathway of gene enrichment was figured out. Next,15 pieces of non-redundant gene enrichment were analyzed on 20 KEGG pathways. Besides, 15 genes were input into String database to draw interaction network diagram, another network diagram for the key genes of enrichment on pathway was also made, the two network diagrams were compared. Results In the two network diagrams, the top-ranked genes in terms of relational hierarchy turned out to be FASLG, FAS, ICAM1, IL1 B, AKT1, STAT3, TGFβ1, IL4 R, IL11 and IL23 A, etc. Conclusion The five genes of STAT3, ICAM1, IL1 B, TGFβ1 and AKT1 have something to do with CAG and an in-depth research should be conducted. Moreover, the diagram which shows the interaction between the pathway and the genes related to CAG should be analyzed, which can do good to the understanding on the pathogenesis of CAG and can provide reliable target for the development of new drug.
Objective By means of DAVID database, the information related to pathway and gene was obtained, the function and distribution of important gene was analyzed, the target gene related to chronic atrophic gastritis(CAG) was screened, so as to promote the research on CAG pathogenesis and the development of new drug. Methods By taking"chronic atrophic gastritis" as key words, the gene related to CAG was retrieved in NCBI database in June 2018 and the obtained gene data was imported into DAVID database, then the pathway of gene enrichment was figured out. Next,15 pieces of non-redundant gene enrichment were analyzed on 20 KEGG pathways. Besides, 15 genes were input into String database to draw interaction network diagram, another network diagram for the key genes of enrichment on pathway was also made, the two network diagrams were compared. Results In the two network diagrams, the top-ranked genes in terms of relational hierarchy turned out to be FASLG, FAS, ICAM1, IL1 B, AKT1, STAT3, TGFβ1, IL4 R, IL11 and IL23 A, etc. Conclusion The five genes of STAT3, ICAM1, IL1 B, TGFβ1 and AKT1 have something to do with CAG and an in-depth research should be conducted. Moreover, the diagram which shows the interaction between the pathway and the genes related to CAG should be analyzed, which can do good to the understanding on the pathogenesis of CAG and can provide reliable target for the development of new drug.
引文
[1]王仲略,周刚,沈慧琳.慢性萎缩性胃炎患者的危险因素与临床治疗效果[J].中华医院感染学杂志,2015,25(8):1817-1819.
[2]魏玮,杨洋.慢性萎缩性胃炎诊治现状及中医药治疗优势[J].中医杂志,2016,57(1):36-40.
[3]魏玮,杨洋,史海霞.慢性萎缩性胃炎中医诊疗现状、挑战及展望[J].中国中西医结合杂志,2015,35(12):1424-1426.
[4]吴建新,张燕,张庆华,等.胃癌与慢性萎缩性胃炎基因表达谱的差异和关联[J].中国癌症杂志,2008,18(2):118-123.
[5]张晓倩,鲁重美.幽门螺杆菌感染、慢性萎缩性胃炎与胃癌[J].临床消化病杂志,2016,28(3):192-195.
[6]Huang da W,Sherman BT,Lempicki RA.Bioinformatics enrichment tools:paths toward the comprehensive functional analysis of large gene lists[J].Nucleic Acids Res,2009,37(1):1-13.
[7]赵秋枫,王实,姜洋,等.基于KEGG通路和基因互作网络对溃疡性结肠炎药靶基因的筛选[J].中华中医药学刊,2016,34(11):2681-2684.
[8]蒋燕明,李力.宫颈上皮内瘤变进展相关基因的生物信息学分析[J].中国肿瘤临床,2016,43(19):840-844.
[9]黄懋敏,董丹丹,亓丹丹,等.慢性萎缩性胃炎患者Hp感染与TGF-βRⅡ、IL-6和TNF-α的表达研究[J].中国免疫学杂志,2018,34(5):751-756.
[10]黄慧,廖文军,粟钰淇,等.TGF-β1、HIF-1α、VEGF在胃癌组织及癌旁组织中的表达及临床意义[J].现代生物医学进展,2014,14(18):3524-3527.
[11]李军祥,陈誩,吕宾,等.慢性萎缩性胃炎中西医结合诊疗共识意见(2017年)[J].中国中西医结合消化杂志,2018,26(2):121-131.
[12]成映霞,段永强,朱立鸣,等.益气健脾活血中药对萎缩性胃炎TNF-α、IL-2和EGF表达的影响[J].中国老年学杂志,2013,33(15):3649-3651.
[13]张静霜,朱西杰,朱微微,等.复方蜥蜴散对慢性萎缩性胃炎模型大鼠肿瘤坏死因子-α及胃黏膜病理组织学的影响[J].时珍国医国药,2010,21(2):286-288.
[14]伍丹丹,董卫国.TNF-α在胃癌发生发展中的作用及治疗研究进展[J].疑难病杂志,2018,17(4):428-432.
[15]黄铭涵,黄健,陈琴,等.健脾清化中药复方对大鼠慢性萎缩性胃炎TLR4-My D88依赖途径蛋白表达及TNF-α的影响[J].中国药理学通报,2016,32(9):1321-1325.
[16]胡欣,万大方.JAK/STAT信号转导途径研究进展及其与肿瘤的关系[J].肿瘤,2005,25(4):404-406.
[17]邓立力,赵玉莹,姜秋颖,等.胃癌细胞中JAK-STAT和ras-MAPK信号通路相关基因的表达及意义[J].肿瘤防治研究,2013,40(11):1027-1030.
[18]蔺焕萍,王巧侠,王小平,等.基于VEGF,STAT3和HIF-1α信号转导分子探讨参佛胃康逆转小鼠慢性萎缩性胃炎癌前病变作用机制[J].时珍国医国药,2017,28(10):2320-2322.
[19]韦维,汪波,万文雅,等.安胃汤干预慢性萎缩性胃炎大鼠JAK/STAT信号传导通路的作用机制[J].中医药导报,2017,23(15):22-26.
[20]王潇,尹天舒,李柏逸,等.基因功能富集分析的研究进展[J].中国科学:生命科学,2016,46(4):363-373.
[2]魏玮,杨洋.慢性萎缩性胃炎诊治现状及中医药治疗优势[J].中医杂志,2016,57(1):36-40.
[3]魏玮,杨洋,史海霞.慢性萎缩性胃炎中医诊疗现状、挑战及展望[J].中国中西医结合杂志,2015,35(12):1424-1426.
[4]吴建新,张燕,张庆华,等.胃癌与慢性萎缩性胃炎基因表达谱的差异和关联[J].中国癌症杂志,2008,18(2):118-123.
[5]张晓倩,鲁重美.幽门螺杆菌感染、慢性萎缩性胃炎与胃癌[J].临床消化病杂志,2016,28(3):192-195.
[6]Huang da W,Sherman BT,Lempicki RA.Bioinformatics enrichment tools:paths toward the comprehensive functional analysis of large gene lists[J].Nucleic Acids Res,2009,37(1):1-13.
[7]赵秋枫,王实,姜洋,等.基于KEGG通路和基因互作网络对溃疡性结肠炎药靶基因的筛选[J].中华中医药学刊,2016,34(11):2681-2684.
[8]蒋燕明,李力.宫颈上皮内瘤变进展相关基因的生物信息学分析[J].中国肿瘤临床,2016,43(19):840-844.
[9]黄懋敏,董丹丹,亓丹丹,等.慢性萎缩性胃炎患者Hp感染与TGF-βRⅡ、IL-6和TNF-α的表达研究[J].中国免疫学杂志,2018,34(5):751-756.
[10]黄慧,廖文军,粟钰淇,等.TGF-β1、HIF-1α、VEGF在胃癌组织及癌旁组织中的表达及临床意义[J].现代生物医学进展,2014,14(18):3524-3527.
[11]李军祥,陈誩,吕宾,等.慢性萎缩性胃炎中西医结合诊疗共识意见(2017年)[J].中国中西医结合消化杂志,2018,26(2):121-131.
[12]成映霞,段永强,朱立鸣,等.益气健脾活血中药对萎缩性胃炎TNF-α、IL-2和EGF表达的影响[J].中国老年学杂志,2013,33(15):3649-3651.
[13]张静霜,朱西杰,朱微微,等.复方蜥蜴散对慢性萎缩性胃炎模型大鼠肿瘤坏死因子-α及胃黏膜病理组织学的影响[J].时珍国医国药,2010,21(2):286-288.
[14]伍丹丹,董卫国.TNF-α在胃癌发生发展中的作用及治疗研究进展[J].疑难病杂志,2018,17(4):428-432.
[15]黄铭涵,黄健,陈琴,等.健脾清化中药复方对大鼠慢性萎缩性胃炎TLR4-My D88依赖途径蛋白表达及TNF-α的影响[J].中国药理学通报,2016,32(9):1321-1325.
[16]胡欣,万大方.JAK/STAT信号转导途径研究进展及其与肿瘤的关系[J].肿瘤,2005,25(4):404-406.
[17]邓立力,赵玉莹,姜秋颖,等.胃癌细胞中JAK-STAT和ras-MAPK信号通路相关基因的表达及意义[J].肿瘤防治研究,2013,40(11):1027-1030.
[18]蔺焕萍,王巧侠,王小平,等.基于VEGF,STAT3和HIF-1α信号转导分子探讨参佛胃康逆转小鼠慢性萎缩性胃炎癌前病变作用机制[J].时珍国医国药,2017,28(10):2320-2322.
[19]韦维,汪波,万文雅,等.安胃汤干预慢性萎缩性胃炎大鼠JAK/STAT信号传导通路的作用机制[J].中医药导报,2017,23(15):22-26.
[20]王潇,尹天舒,李柏逸,等.基因功能富集分析的研究进展[J].中国科学:生命科学,2016,46(4):363-373.