Epstein-Barr Virus-associated Gastric Cancer: Disease That Requires Special Approach

Overview

Journal Gastric Cancer

Specialties Gastroenterology
Oncology

Date 2020 Jun 10

PMID 32514646

Citations 24

Authors

Ekaterina Ignatova

Daria Seriak

Mikhail Fedyanin

Alexey Tryakin

Ilya Pokataev

Sofia Menshikova

Yuliya Vakhabova

Ksenia Smirnova

Sergey Tjulandin

Jaffer A Ajani

Affiliations

Soon will be listed here.

Abstract

Epstein-Barr virus-associated gastric cancer [EBV-associated GC, EBV( +) GC] is a distinct molecular subtype of gastrointestinal (GI) cancers. It accounts for up to 10% of all molecular subtypes of gastric cancer (GC). It has unique genetic and epigenetic features, which determine its definitive phenotype with male and younger age predominance, proximal stomach localization, and diffuse adenocarcinoma histology. EBV( +) GC also has a unique epigenetic profile and mutational status with frequent mutations of PIK3CA, ARID1A and BCOR, and PD-L1 and PD-L2 amplifications, as well. The aim of this review is to highlight clinical significance of EBV( +) GC and prognostic role of EBV infection, and to determine potentially appropriate drug therapy for this disease.

Citing Articles

Interplay of aurora kinase a functional residues and Epstein-barr Nuclear Antigen 1 in Epstein-barr virus associated Gastric cancer using AGS cells.

Varshney N, Singh S, Kandpal M, Saini V, Roberston E, Jha H BMC Cancer. 2025; 25(1):143.

PMID: 39856614 PMC: 11762537. DOI: 10.1186/s12885-024-13260-z.

Association of PD-L1 positivity with Epstein Barr virus infection and microsatellite instability in gastric carcinomas with lymphoid stroma.

Lee S, Oh H Sci Rep. 2024; 14(1):30932.

PMID: 39730741 PMC: 11680954. DOI: 10.1038/s41598-024-81764-6.

The landscape of 142 Epstein-Barr viral whole genomes in gastric cancer.

Kojima Y, Hamada M, Naruse A, Goto K, Khine H, Arai H J Gastroenterol. 2024; 60(1):55-65.

PMID: 39572460 DOI: 10.1007/s00535-024-02170-3.

Low EBI3 Expression Promotes the Malignant Degree of Gastric Cancer.

Gu Q, Wu H, Cheng Z, Zhi X, Song Q, Chen X Dis Markers. 2024; 2022:5588043.

PMID: 39291183 PMC: 11407894. DOI: 10.1155/2022/5588043.

The Epstein-Barr virus-miRNA-BART6-5p regulates TGF-β/SMAD4 pathway to induce glycolysis and enhance proliferation and metastasis of gastric cancer cells.

Zhao X, Huang X, Dang C, Wang X, Qi Y, Li H Oncol Res. 2024; 32(5):999-1009.

PMID: 38686046 PMC: 11055990. DOI: 10.32604/or.2024.046679.

References

Akiba S, Koriyama C, Herrera-Goepfert R, Eizuru Y . Epstein-Barr virus associated gastric carcinoma: epidemiological and clinicopathological features. Cancer Sci. 2008; 99(2):195-201. PMC: 11158035. DOI: 10.1111/j.1349-7006.2007.00674.x. View

Liu Y, Sethi N, Hinoue T, Schneider B, Cherniack A, Sanchez-Vega F . Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas. Cancer Cell. 2018; 33(4):721-735.e8. PMC: 5966039. DOI: 10.1016/j.ccell.2018.03.010. View

Fukayama M . Epstein-Barr virus and gastric carcinoma. Pathol Int. 2010; 60(5):337-50. DOI: 10.1111/j.1440-1827.2010.02533.x. View

Yanai H, Nishikawa J, Mizugaki Y, Shimizu N, Takada K, Matsusaki K . Endoscopic and pathologic features of Epstein-Barr virus-associated gastric carcinoma. Gastrointest Endosc. 1997; 45(3):236-42. DOI: 10.1016/s0016-5107(97)70265-7. View

Nishikawa J, Yanai H, Mizugaki Y, Takada K, Tada M, Okita K . Case report: hypoechoic submucosal nodules: a sign of Epstein-Barr virus-associated early gastric cancer. J Gastroenterol Hepatol. 1998; 13(6):585-90. DOI: 10.1111/j.1440-1746.1998.tb00694.x. View

Yanai H, Chihara D, Harano M, Sakaguchi E, Murakami T, Nishikawa J . Epstein-Barr Virus-associated Early Gastric Cancer Treated with Endoscopic Submucosal Dissection: A Possible Candidate for Extended Criteria of Endoscopic Submucosal Dissection. Intern Med. 2019; 58(22):3247-3250. PMC: 6911759. DOI: 10.2169/internalmedicine.3055-19. View

Koh J, Ock C, Kim J, Nam S, Kwak Y, Yun S . Clinicopathologic implications of immune classification by PD-L1 expression and CD8-positive tumor-infiltrating lymphocytes in stage II and III gastric cancer patients. Oncotarget. 2017; 8(16):26356-26367. PMC: 5432263. DOI: 10.18632/oncotarget.15465. View

Derks S, Liao X, Chiaravalli A, Xu X, Camargo M, Solcia E . Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers. Oncotarget. 2016; 7(22):32925-32. PMC: 5078063. DOI: 10.18632/oncotarget.9076. View

Spear P, Longnecker R . Herpesvirus entry: an update. J Virol. 2003; 77(19):10179-85. PMC: 228481. DOI: 10.1128/jvi.77.19.10179-10185.2003. View

10.

Chesnokova L, Hutt-Fletcher L . Epstein-Barr virus infection mechanisms. Chin J Cancer. 2014; 33(11):545-8. PMC: 4244317. DOI: 10.5732/cjc.014.10168. View

11.

Fukayama M, Hayashi Y, Iwasaki Y, Chong J, Ooba T, Takizawa T . Epstein-Barr virus-associated gastric carcinoma and Epstein-Barr virus infection of the stomach. Lab Invest. 1994; 71(1):73-81. View

12.

Frappier L . Contributions of Epstein-Barr nuclear antigen 1 (EBNA1) to cell immortalization and survival. Viruses. 2012; 4(9):1537-1547. PMC: 3499818. DOI: 10.3390/v4091537. View

13.

Chen C, Li D, Guo N . Regulation of cellular and viral protein expression by the Epstein-Barr virus transcriptional regulator Zta: implications for therapy of EBV associated tumors. Cancer Biol Ther. 2009; 8(11):987-95. DOI: 10.4161/cbt.8.11.8369. View

14.

Matsusaka K, Funata S, Fukuyo M, Seto Y, Aburatani H, Fukayama M . Epstein-Barr virus infection induces genome-wide de novo DNA methylation in non-neoplastic gastric epithelial cells. J Pathol. 2017; 242(4):391-399. DOI: 10.1002/path.4909. View

15.

Fernandez A, Rosales C, Lopez-Nieva P, Grana O, Ballestar E, Ropero S . The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer. Genome Res. 2009; 19(3):438-51. PMC: 2661803. DOI: 10.1101/gr.083550.108. View

16.

Hino R, Uozaki H, Murakami N, Ushiku T, Shinozaki A, Ishikawa S . Activation of DNA methyltransferase 1 by EBV latent membrane protein 2A leads to promoter hypermethylation of PTEN gene in gastric carcinoma. Cancer Res. 2009; 69(7):2766-74. DOI: 10.1158/0008-5472.CAN-08-3070. View

17.

Shinozaki-Ushiku A, Kunita A, Isogai M, Hibiya T, Ushiku T, Takada K . Profiling of Virus-Encoded MicroRNAs in Epstein-Barr Virus-Associated Gastric Carcinoma and Their Roles in Gastric Carcinogenesis. J Virol. 2015; 89(10):5581-91. PMC: 4442544. DOI: 10.1128/JVI.03639-14. View

18.

Gu J, Qian H, Shen L, Zhang X, Zhu W, Huang L . Gastric cancer exosomes trigger differentiation of umbilical cord derived mesenchymal stem cells to carcinoma-associated fibroblasts through TGF-β/Smad pathway. PLoS One. 2013; 7(12):e52465. PMC: 3527492. DOI: 10.1371/journal.pone.0052465. View

19.

Samuels Y, Waldman T . Oncogenic mutations of PIK3CA in human cancers. Curr Top Microbiol Immunol. 2010; 347:21-41. PMC: 3164550. DOI: 10.1007/82_2010_68. View

20.

Yuen J, Chung G, Lun S, Cheung C, To K, Lo K . Epigenetic inactivation of inositol polyphosphate 4-phosphatase B (INPP4B), a regulator of PI3K/AKT signaling pathway in EBV-associated nasopharyngeal carcinoma. PLoS One. 2014; 9(8):e105163. PMC: 4134277. DOI: 10.1371/journal.pone.0105163. View