Deciphering the Differences Between Epstein–Barr Virus‐Associated and Negative Gastric Cancer in the Prospect of CDKN2A Genomic Alterations and Lymphoid Infiltration

ABSTRACT Background Gastric cancer (GC) is a major health concern worldwide. One important contributing factor is the presence of the Epstein‐Barr virus (EBV). However, the molecular pattern of how EBV participates in the malignant transition process remains unclear. Methods GC samples were stained...

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Main Authors: Fuda Xie, Bonan Chen, Yang Lyu, Peiyao Yu, Canbin Fang, Kam Tong Leung, Shouyu Wang, Dazhi Xu, Jun Yu, Kwok Wai Lo, Ka Fai To, Wei Kang
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.70409
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author Fuda Xie
Bonan Chen
Yang Lyu
Peiyao Yu
Canbin Fang
Kam Tong Leung
Shouyu Wang
Dazhi Xu
Jun Yu
Kwok Wai Lo
Ka Fai To
Wei Kang
author_facet Fuda Xie
Bonan Chen
Yang Lyu
Peiyao Yu
Canbin Fang
Kam Tong Leung
Shouyu Wang
Dazhi Xu
Jun Yu
Kwok Wai Lo
Ka Fai To
Wei Kang
author_sort Fuda Xie
collection DOAJ
description ABSTRACT Background Gastric cancer (GC) is a major health concern worldwide. One important contributing factor is the presence of the Epstein‐Barr virus (EBV). However, the molecular pattern of how EBV participates in the malignant transition process remains unclear. Methods GC samples were stained by immunohistochemistry, fluorescent and EBV‐encoded small RNA in situ hybridization to identify CD8 expression, CDKN2A genomic alteration, and EBV existence. Functional potentials of EBV infection were predicted by bioinformatic enrichment analysis. Results CDKN2A genestayed intact in all EBV‐associated GC cases. Meanwhile, CDKN2A deletion (8.43% cases) was exclusive to EBV‐negative GC cases. Furthermore, EBV infection was positively correlated with CD8+T cell infiltration, and both of them predicted better prognosis. Conclusion This study highlighted the comprehensive impact of EBV infection in GC formation and proposed a thought‐provoking observation for further investigation into the roles of CDKN2A and EBV infection in gastric tumorigenesis.
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series Cancer Medicine
spelling doaj-art-de5dedef4e3d495a823dc1d6010c69572025-01-24T08:46:07ZengWileyCancer Medicine2045-76342025-01-01142n/an/a10.1002/cam4.70409Deciphering the Differences Between Epstein–Barr Virus‐Associated and Negative Gastric Cancer in the Prospect of CDKN2A Genomic Alterations and Lymphoid InfiltrationFuda Xie0Bonan Chen1Yang Lyu2Peiyao Yu3Canbin Fang4Kam Tong Leung5Shouyu Wang6Dazhi Xu7Jun Yu8Kwok Wai Lo9Ka Fai To10Wei Kang11Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong SAR ChinaDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong SAR ChinaDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong SAR ChinaDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong SAR ChinaDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong SAR ChinaDepartment of Pediatrics The Chinese University of Hong Kong Hong Kong SAR ChinaDepartment of Hepatobiliary Surgery The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing ChinaDepartment of Gastric Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College Fudan University Shanghai ChinaInstitute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Science The Chinese University of Hong Kong Hong Kong SAR ChinaDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong SAR ChinaDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong SAR ChinaDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong SAR ChinaABSTRACT Background Gastric cancer (GC) is a major health concern worldwide. One important contributing factor is the presence of the Epstein‐Barr virus (EBV). However, the molecular pattern of how EBV participates in the malignant transition process remains unclear. Methods GC samples were stained by immunohistochemistry, fluorescent and EBV‐encoded small RNA in situ hybridization to identify CD8 expression, CDKN2A genomic alteration, and EBV existence. Functional potentials of EBV infection were predicted by bioinformatic enrichment analysis. Results CDKN2A genestayed intact in all EBV‐associated GC cases. Meanwhile, CDKN2A deletion (8.43% cases) was exclusive to EBV‐negative GC cases. Furthermore, EBV infection was positively correlated with CD8+T cell infiltration, and both of them predicted better prognosis. Conclusion This study highlighted the comprehensive impact of EBV infection in GC formation and proposed a thought‐provoking observation for further investigation into the roles of CDKN2A and EBV infection in gastric tumorigenesis.https://doi.org/10.1002/cam4.70409CD8+ T cell infiltrationCDKN2AEpstein–Barr virusgastric cancer
spellingShingle Fuda Xie
Bonan Chen
Yang Lyu
Peiyao Yu
Canbin Fang
Kam Tong Leung
Shouyu Wang
Dazhi Xu
Jun Yu
Kwok Wai Lo
Ka Fai To
Wei Kang
Deciphering the Differences Between Epstein–Barr Virus‐Associated and Negative Gastric Cancer in the Prospect of CDKN2A Genomic Alterations and Lymphoid Infiltration
Cancer Medicine
CD8+ T cell infiltration
CDKN2A
Epstein–Barr virus
gastric cancer
title Deciphering the Differences Between Epstein–Barr Virus‐Associated and Negative Gastric Cancer in the Prospect of CDKN2A Genomic Alterations and Lymphoid Infiltration
title_full Deciphering the Differences Between Epstein–Barr Virus‐Associated and Negative Gastric Cancer in the Prospect of CDKN2A Genomic Alterations and Lymphoid Infiltration
title_fullStr Deciphering the Differences Between Epstein–Barr Virus‐Associated and Negative Gastric Cancer in the Prospect of CDKN2A Genomic Alterations and Lymphoid Infiltration
title_full_unstemmed Deciphering the Differences Between Epstein–Barr Virus‐Associated and Negative Gastric Cancer in the Prospect of CDKN2A Genomic Alterations and Lymphoid Infiltration
title_short Deciphering the Differences Between Epstein–Barr Virus‐Associated and Negative Gastric Cancer in the Prospect of CDKN2A Genomic Alterations and Lymphoid Infiltration
title_sort deciphering the differences between epstein barr virus associated and negative gastric cancer in the prospect of cdkn2a genomic alterations and lymphoid infiltration
topic CD8+ T cell infiltration
CDKN2A
Epstein–Barr virus
gastric cancer
url https://doi.org/10.1002/cam4.70409
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