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

Ruiyuan Zhang,Yao-Zhong Liu,Melody Baddoo,Michael J Strong,Erik K Flemington,Zhen Lin,Yu-Ping Wang

doi:10.18632/oncotarget.16417

Abstract

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.

Highlights

Gastric carcinoma (GC) is the fifth most common cancer and the third leading cause of mortality from cancers in the world [1]
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
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

Summary

Introduction

Gastric carcinoma (GC) is the fifth most common cancer and the third leading cause of mortality from cancers in the world [1]. EBV (Epstein–Barr virus) infection is one of the most important factors that cause GC [2, 4]. EBV is a cancer-related virus, which was observed to cause various human cancers in epithelial cells, lymphocytes and mesenchymal cells [5,6,7] and was found to account for 10% of all cases of GC [2, 4]. GC that was related to EBV infection shows a distinct molecular character compared to GC caused by other factors [4]. A recent study [4] in TCGA (The Cancer Genome Atlas) characterized GC into 4 subtypes: EBV−positive (EBV+), Microsatellite instability (MSI), genomically stable, and chromosomal instable. The EBV+ subtype was shown to have extensive DNA promoter hypermethylation [4]

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