增殖期婴儿血管瘤mRNA表达谱分析及信号网络构建
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摘要
目的:分析增殖期婴儿血管瘤(IH)mRNA表达谱,并构建增殖期婴儿血管瘤调控的信号通路网络。方法:收集2017年3月—2017年9月西安交通大学第二附属医院小儿外科手术治疗的9例IH患儿手术切除标本,依据分期不同分为增生期组(n=5)和消退期组(n=4),病例均经病理确诊,比较两组mRNA表达谱差异,分析两组差异基因的GO(Gene Ontology)以及两组主要差异基因信号通路变化。结果:通过GO富集分析得出差异基因在基因的分子功能(MF),参与的生物过程(BP)和所处于的细胞组成(CC)三大类信息中的分布,成功构建GO富集功能图;通过KEGG数据库进行Pathway注释,筛选出差异基因、靶基因富集的显著性信号通路,根据信号通路间的关联关系成功构建Pathway之间的信号转导网络。结论:基因芯片方法检测增殖期和消退期mRNA表达谱可成功筛选差异基因,GO富集分析、KEGG数据库注释等生物信息学方法可通过差异基因筛选出显著性信号调控通路,并构建信号转导网络。
Objective: To analyze the mRNA expression profile of proliferating infantile hemangioma (IH) and construct a signaling pathway network for regulation of proliferating IH. Methods: The surgical specimens of 9 infants with IH treated by surgery in pediatric surgery department of the Second Affiliated Hospital of Xi'an Jiaotong University from March 2017 to September 2017 were collected. They were divided into the proliferative group(n=5) and the regressive group(n=4) according to different stages. The cases were confirmed by pathological section and HE staining. The mRNA expression profile was compared between the two groups, and the GO(gene ontology) of differential genes and changes of major differential gene signaling pathways were analyzed. Results: The distribution of differential genes in the three major categories of information molecular function(MF), involved biological processes(BP) and cellular composition(CC) was obtained through GO enrichment analysis, and the GO enrichment function map was successfully constructed. Pathway annotation was performed through KEGG database, and the significant signal pathways of differential gene and target gene enrichment were screened out. The signal transduction network between Pathway was successfully constructed according to the relationship between signaling pathways. Conclusion: The gene chip method can detect the mRNA expression profiles in proliferative and regressive stages, which helps successful screening of differential genes. The bioinformatic methods such as GO enrichment analysis and KEGG database annotation can screen out significant signal regulatory pathways through differential genes and construct a signal transduction network.
Objective: To analyze the mRNA expression profile of proliferating infantile hemangioma (IH) and construct a signaling pathway network for regulation of proliferating IH. Methods: The surgical specimens of 9 infants with IH treated by surgery in pediatric surgery department of the Second Affiliated Hospital of Xi'an Jiaotong University from March 2017 to September 2017 were collected. They were divided into the proliferative group(n=5) and the regressive group(n=4) according to different stages. The cases were confirmed by pathological section and HE staining. The mRNA expression profile was compared between the two groups, and the GO(gene ontology) of differential genes and changes of major differential gene signaling pathways were analyzed. Results: The distribution of differential genes in the three major categories of information molecular function(MF), involved biological processes(BP) and cellular composition(CC) was obtained through GO enrichment analysis, and the GO enrichment function map was successfully constructed. Pathway annotation was performed through KEGG database, and the significant signal pathways of differential gene and target gene enrichment were screened out. The signal transduction network between Pathway was successfully constructed according to the relationship between signaling pathways. Conclusion: The gene chip method can detect the mRNA expression profiles in proliferative and regressive stages, which helps successful screening of differential genes. The bioinformatic methods such as GO enrichment analysis and KEGG database annotation can screen out significant signal regulatory pathways through differential genes and construct a signal transduction network.
引文
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[8]Giachetti A,Sojo MM,Garcia-Monaco R.Infantile hemangiomas[J].Arch Argent Pediatr,2013,111(6):537-545.
[9]王胜,王胜春,李琳,等.EGFL-7介导的促血管生成作用在婴幼儿血管瘤中的作用及干预分析[J].重庆医学,2018,31(9):1218-1220.
[10]徐建国,邢新,方硕,等.VEGF信号通路在婴幼儿血管瘤中的作用研究进展[J].中华整形外科杂志,2015,31(4):314-318.
[11]Ji Y,Chen S,Li K,et al.Signaling pathways in the development of infant ile hemangioma[J].J Hematol Oncol,2014,7:13.
[12]杨开颖,陈思源,吉毅.婴儿血管瘤发病过程中的关键信号通路[J].国际皮肤性病学杂志,2017,43(6):369-373.
[13]刘盛秀.Notch信号通路在婴儿血管瘤发病机制中的作用[J].国际皮肤性病学杂志,2017,43(4):235-237.
[2]Ritter MR,Butschek RA,Martin F,et al.Pathogenesis of infantile haem angioma:new molecular and cellular insights[J].Exp Rev Mol Med,2007,9(32):1-19.
[3]武会芝,李勇,王霞,等.β-受体阻滞药治疗婴幼儿血管瘤作用机制的研究进展[J].中国药房,2016,27(8):1143-1146.
[4]王静,赵卓,王艳红,等.辽宁省婴幼儿血管瘤及其相关因素的Logistic回归分析[J].中国皮肤性病学杂志,2017,32(6):619-622.
[5]金玲琴,罗宏宾,曹毅.婴幼儿血管瘤药物治疗进展[J].中国皮肤性病学杂志,2016,19(5):520-523.
[6]朱雅琳,侯巍,帕丽达·阿布利孜,等.普萘洛尔及异丙肾上腺素对体外培养婴儿血管瘤内皮细胞增殖和血管内皮生长因子、碱性成纤维细胞生长因子表达的影响[J].中华皮肤科杂志,2016,(3):158-162.
[7]曹国锋,龚沛淳.Notch信号通路在普萘洛尔抑制婴幼儿血管瘤周细胞中的作用[J].中华整形外科杂志,2017,33(6):445-449.
[8]Giachetti A,Sojo MM,Garcia-Monaco R.Infantile hemangiomas[J].Arch Argent Pediatr,2013,111(6):537-545.
[9]王胜,王胜春,李琳,等.EGFL-7介导的促血管生成作用在婴幼儿血管瘤中的作用及干预分析[J].重庆医学,2018,31(9):1218-1220.
[10]徐建国,邢新,方硕,等.VEGF信号通路在婴幼儿血管瘤中的作用研究进展[J].中华整形外科杂志,2015,31(4):314-318.
[11]Ji Y,Chen S,Li K,et al.Signaling pathways in the development of infant ile hemangioma[J].J Hematol Oncol,2014,7:13.
[12]杨开颖,陈思源,吉毅.婴儿血管瘤发病过程中的关键信号通路[J].国际皮肤性病学杂志,2017,43(6):369-373.
[13]刘盛秀.Notch信号通路在婴儿血管瘤发病机制中的作用[J].国际皮肤性病学杂志,2017,43(4):235-237.