Interpretation of EBV Infection in Pan-cancer Genome Considering Viral Life Cycle: LiEB (Life Cycle of Epstein-Barr Virus)

Overview

Journal Sci Rep

Specialty Science

Date 2019 Mar 7

PMID 30837539

Citations 10

Authors

Hyojin Song

Yoojoo Lim

Hogune Im

Jeong Mo Bae

Gyeong Hoon Kang

Junhak Ahn

Daehyun Baek

Tae-You Kim

Sung-Soo Yoon

Youngil Koh

Affiliations

Soon will be listed here.

Abstract

We report a novel transcriptomic analysis workflow called LiEB (Life cycle of Epstein-Barr virus) to characterize distributions of oncogenic virus, Epstein-Barr virus (EBV) infection in human tumors. We analyzed 851 The Cancer Genome Atlas whole-transcriptome sequencing (WTS) data to investigate EBV infection by life cycle information using three-step LiEB workflow: 1) characterize virus infection generally; 2) align transcriptome sequences against a hybrid human-EBV genome, and 3) quantify EBV gene expression. Our results agreed with EBV infection status of public cell line data. Analysis in stomach adenocarcinoma identified EBV-positive cases involving PIK3CA mutations and/or CDKN2A silencing with biologically more determination, compared to previous reports. In this study, we found that a small number of colorectal adenocarcinoma cases involved with EBV lytic gene expression. Expression of EBV lytic genes was also observed in 3% of external colon cancer cohort upon WTS analysis. Gene set enrichment analysis showed elevated expression of genes related to E2F targeting and interferon-gamma responses in EBV-associated tumors. Finally, we suggest that interpretation of EBV life cycle is essential when analyzing its infection in tumors, and LiEB provides high capability of detecting EBV-positive tumors. Observation of EBV lytic gene expression in a subset of colon cancers warrants further research.

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