Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jun 7;18(6):e0283366.
doi: 10.1371/journal.pone.0283366. eCollection 2023.

Does Epstein-Barr virus-positive gastric cancer establish a significant relationship with the multiple genes related to gastric carcinogenesis?

Ji Won Seo  1 , Ki Bum Park  1 , Hyung Min Chin  1 , Kyong Hwa Jun  1
Affiliations

Does Epstein-Barr virus-positive gastric cancer establish a significant relationship with the multiple genes related to gastric carcinogenesis?

Ji Won Seo et al. PLoS One. .

Abstract

Gastric cancer has been categorized into molecular subtypes including Epstein-Barr virus (EBV)-positive tumors, which provide clinicopathological and prognostic information. In this study, we investigated the EBV infection status of patients with gastric cancer and its correlation with the clinicopathological characteristics and multiple genes related to gastric carcinogenesis. The data of 460 gastric cancer patients who underwent curative gastrectomy with D2 lymph node dissection between January 2017 and February 2022 were analyzed. The clinicopathological features and prognosis of the patients with EBV-positive gastric cancers were compared with those of EBV-negative gastric cancers. Immunohistochemistry for epidermal growth factor receptor (EGFR), C-erb B2, Ki-67, and p53 was performed. Additionally, in situ hybridization was conducted to detect EBV, and microsatellite instability (MSI) analysis was used to assess the deficiency in mismatch repair (MMR) genes. EBV-positivity and MSI were identified in 10.4% and 37.3% of gastric cancer patients, respectively. EBV positivity was associated with male gender (P = 0.001), proximal location (P = 0.004), poorly differentiated histological type (P = 0.048), moderate to severe lymphoid stroma (P = 0.006), high Ki-67 expression (P = 0.02), and a shorter resection margin. EGFR was more often expressed in EBV-negative gastric cancers (P < 0.001). MSI tumors were associated with older age (P = 0.01), the presence of lymphatic invasion (P = 0.02), less perineural invasion (P = 0.05), and the presence of H. pylori infection (P = 0.05). EBV positive gastric cancer is associated with increased Ki-67 and decreased EGFR expression and a shorter resection margin due to the prominent lymphoid stroma. However, MMR deficiency is not associated with EBV status even though MSI gastric cancer is related to H. pylori status.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Kaplan–Meier survival curve analysis.
Advanced TNM stage was associated with poor overall survival (OS).) in patients with gastric adenocarcinoma (P < 0.001 and P < 0.001, respectively).
Fig 2
Fig 2. Meier survival curve analysis.
Kaplan– Advanced TNM stage was associated with poor disease-free survival (DFS) in patients with gastric adenocarcinoma (P < 0.001 and P < 0.001, respectively).
Fig 3
Fig 3. Kaplan-Meier survival curve analysis.
OS of gastric cancer patients according to EBV status.
Fig 4
Fig 4. Kaplan-Meier survival curve analysis.
DFS of gastric cancer patients according to EBV status.
Fig 5
Fig 5. Kaplan-Meier survival curve analysis.
OS of gastric cancer patients according to MSI status.
Fig 6
Fig 6. Kaplan-Meier survival curve analysis.
DFS of gastric cancer patients according to MSI status.
See this image and copyright information in PMC

References

    1. Sekiguchi M, Oda I, Matsuda T, Saito Y. Epidemiological trends and future perspectives of gastric cancer in Eastern Asia. Digestion. 2021;103(1):22–8. doi: 10.1159/000518483 - DOI - PubMed
    1. Lee J, Lim DH, Kim S, Park SH, Park JO, Park YS, et al.. Phase III trial comparing Capecitabine plus Cisplatin versus Capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: The artist trial. Journal of Clinical Oncology. 2012;30(3):268–73. doi: 10.1200/JCO.2011.39.1953 - DOI - PubMed
    1. Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, et al.. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. New England Journal of Medicine. 2007;357(18):1810–20. doi: 10.1056/NEJMoa072252 - DOI - PubMed
    1. Sohn BH, Hwang J-E, Jang H-J, Lee H-S, Oh SC, Shim J-J, et al.. Clinical significance of four molecular subtypes of gastric cancer identified by the cancer genome atlas project. Clinical Cancer Research. 2017;23(15):4441–9. doi: 10.1158/1078-0432.CCR-16-2211 - DOI - PMC - PubMed
    1. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202–9. doi: 10.1038/nature13480 - DOI - PMC - PubMed