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Deregulation of Immune Response Genes in Patients With Epstein-Barr Virus-Associated Gastric Cancer and Outcomes

Title
Deregulation of Immune Response Genes in Patients With Epstein-Barr Virus-Associated Gastric Cancer and Outcomes
Authors
Kim, Sun YoungPark, CharnyKim, Ha-JungPark, JihyunHwang, JinhaKim, Jong-IlChoi, Min GewKim, SungKim, Kyoung-MeeKang, Myung-Soo
Ewha Authors
박찬이
SCOPUS Author ID
박찬이scopus
Issue Date
2015
Journal Title
GASTROENTEROLOGY
ISSN
0016-5085JCR Link1528-0012JCR Link
Citation
vol. 148, no. 1, pp. 137 - U574
Keywords
Anti-Tumor ImmunityViral InfectionSurvivalStomach Cancer
Publisher
W B SAUNDERS CO-ELSEVIER INC
Indexed
SCI; SCIE; SCOPUS WOS
Abstract
BACKGROUND & AIMS: Patients with Epstein-Barr virus-associated gastric carcinoma (EBVaGC) have a better prognosis than those with gastric cancer not associated with EBV infection (EBVnGC). This is partly because EBV infection recruits lymphocytes, which infiltrate the tumor. A high degree of tumor heterogeneity is likely to be associated with poor response. We investigated differences in gene expression patterns between EBVaGC and EBVnGC. METHODS: We used gene expression profile analysis to compare tumor and nontumor gastric tissues from 12 patients with EBVaGC and 14 patients with EBVnGC. Findings were validated by whole transcriptome RNAseq and real-time quantitative polymerase chain reaction analyses. CD3(+) primary T cells were isolated from human blood samples; migration of these cells and of Jurkat cells were measured in culture with EBV-infected and uninfected gastric cancer cells. RESULTS: Based on Pearson correlation matrix analysis, EBVaGCs had a higher degree of homogeneity than EBVnGCs. Although 4550 genes were differentially expressed between tumor and nontumor gastric tissues of patients with EBVnGC, only 186 genes were differentially expressed between tumor and nontumor gastric tissues of patients with EBVaGC (P < .001). This finding supports the concept that EBVaGCs have fewer genetic and epigenetic alterations than EBVnGCs. Expression of major histocompatibility complex class II genes and genes that regulate chemokine activity were more often deregulated in EBVaGCs compared with nontumor tissues. In culture, more T cells migrated to EBV-infected gastric cancer cells than to uninfected cells; migration was blocked with a neutralizing antibody against CXCR3 (a receptor for many chemokines). CONCLUSIONS: Fewer genes are deregulated in EBVaGC than in EBVnGC. Most changes in EBVaGCs occur in immune response genes. These changes might allow EBVaGC to recruit reactive immune cells; this might contribute to the better outcomes of these patients compared with those with EBVnGC.
DOI
10.1053/j.gastro.2014.09.020
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연구기관 > 시스템생물학연구소 > Journal papers
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