Interaction of Epstein-Barr virus genes with human gastric carcinoma transcriptome.

Interaction of Epstein-Barr virus genes with human gastric carcinoma transcriptome.
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DOI:
10.18632/oncotarget.16417
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发表时间:
2017-06-13
期刊:
影响因子:
--
通讯作者:
Liu YZ
Liu YZ
中科院分区:
其他
文献类型:
--
作者:
Zhang R;Strong MJ;Baddoo M;Lin Z;Wang YP;Flemington EK;Liu YZ

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胃癌(GC)是导致死亡的主要原因。10%的胃癌病例与EBV (eb病毒)感染有关。EBV基因在GC中的具体作用机制,特别是病毒基因与人基因的相互作用尚不清楚。在本研究中,从TCGA (The Cancer Genome Atlas)下载了285个GC样品的原始fastq数据,其中包括25个EBV阳性(EBV+) GC样品和260个EBV阴性(EBV -) GC样品。基于RNA-seq生成了人类基因(所有样本)和EBV基因(25个EBV+样本)的表达数据。通过生物信息学分析,鉴定EBV+和EBV -样品中的差异表达(DEx)人类基因和DEx KEGG通路,以及DEx基因中共同表达的人类基因模块和枢纽基因。在EBV+样本中,分析EBV基因表达与人类基因表达模块、EBV基因表达与人类枢纽基因、EBV基因表达与DEx人类途径之间的相关性。EBV基因LMP-1、BALF1和BALF2与人类中心基因CNTD2和VANGL2有显著相关性。EBV基因BALF4和BALF5被发现与人类信号通路相关,包括Jak-STAT信号和磷脂酰肌醇信号系统。我们的研究揭示了EBV与人类GC转录组之间的协调表达模式,并确定了几个关键的EBV基因,这些基因可能通过与人类基因和途径的相互作用在EBV+ GC发病中起重要作用。
Gastric carcinoma (GC) is a leading cause of mortality. 10% of GC cases are related with EBV (Epstein-Barr virus) infection. The detailed mechanistic roles EBV genes play and especially the interaction between the viral genes and human genes in GC remain unclear. In this study, raw fastq data from 285 GC samples were downloaded from TCGA (The Cancer Genome Atlas), including 25 EBV positive (EBV+) GC samples and 260 EBV negative (EBV−) GC samples. RNA-seq based expression data were generated for both human genes (among all the samples) and for the EBV genes (among the 25 EBV+ samples). Bioinformatics analyses were performed to identify differentially expressed (DEx) human genes and DEx KEGG pathways in EBV+ vs. EBV− samples and co-expressed human gene modules and hub genes among the DEx genes. Within the EBV+ samples, analyses were conducted to find correlation between EBV gene expression and the human gene expression modules, between EBV gene expression and the human hub genes, and between EBV gene expression and the DEx human pathways. EBV genes LMP-1, BALF1 and BALF2 were found to have significant correlation with human hub genes, CNTD2 and VANGL2. EBV genes BALF4 and BALF5 were found to correlate with human pathways, including Jak-STAT signaling and Phosphatidylinositol Signaling System. Our study has revealed the coordinated expression patterns between EBV and human GC transcriptome and identified several key EBV genes that may play an important role in EBV+ GC pathogenesis through their interactions with human genes and pathways.
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