Evidence map›Paper›PMID 34493320›Full record

ArticleGenome medicine2021

The genomic architecture of EBV and infected gastric tissue from precursor lesions to carcinoma.

Zhang-Hua Chen, Shu-Mei Yan, Xi-Xi Chen, Qi Zhang, Shang-Xin Liu, Yang Liu, Yi-Ling Luo, Chao Zhang, Miao Xu, Yi-Fan Zhao and 14 more

Open access · goldAbstract read
In one paragraph

Article in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.2field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 35 citations in OpenAlex.

  1. Review
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  3. Comprehensive analysis of the gastric metatranscriptome reveals specific viral signatures associated with gastric cancer.International microbiology : the official journal of the Spanish Society for Microbiology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 4 institutions in 2 countries.

Zhang-Hua Chen *Biomedical Pioneering Innovation Center (BIOPIC), Integrated Research Building Room 330, School of Life Sciences, Peking University, Yiheyuan Road No.5, Haidian District, Beijing, 100871, China.
Shu-Mei Yan *State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Xi-Xi Chen *Biomedical Pioneering Innovation Center (BIOPIC), Integrated Research Building Room 330, School of Life Sciences, Peking University, Yiheyuan Road No.5, Haidian District, Beijing, 100871, China.
Qi Zhang *State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Shang-Xin Liu *State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Yang LiuBiomedical Pioneering Innovation Center (BIOPIC), Integrated Research Building Room 330, School of Life Sciences, Peking University, Yiheyuan Road No.5, Haidian District, Beijing, 100871, China.
Yi-Ling LuoState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Chao ZhangInstitute for Computational Biomedicine, Weill Cornell Medicine, New York, USA.
Miao XuState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Yi-Fan ZhaoBiomedical Pioneering Innovation Center (BIOPIC), Integrated Research Building Room 330, School of Life Sciences, Peking University, Yiheyuan Road No.5, Haidian District, Beijing, 100871, China.
Li-Yun HuangState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Bin-Liu LiuState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Tian-Liang XiaState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Da-Zhi XuDepartment of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
Yao LiangDepartment of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
Yong-Ming ChenDepartment of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
Wei WangDepartment of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
Shu-Qiang YuanDepartment of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
Hui-Zhong ZhangState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Jing-Ping YunState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Wei-Wei ZhaiKey Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Mu-Sheng ZengState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Fan BaiBiomedical Pioneering Innovation Center (BIOPIC), Integrated Research Building Room 330, School of Life Sciences, Peking University, Yiheyuan Road No.5, Haidian District, Beijing, 100871, China. fbai@pku.edu.cn.
Qian ZhongState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. zhongqian@sysucc.org.cn.ORCID 0000-0003-1071-6996
Sun Yat-sen University · CNPeking University · CNChinese Academy of Sciences · CNCornell University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEpstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) present unique molecular signatures, but the tumorigenesis of EBVaGCs and the role EBV plays during this process remain poorly understood.

methodsWe applied whole-exome sequencing, EBV genome sequencing, and whole-genome bisulfite sequencing to multiple samples (n = 123) derived from the same patients (n = 25), which covered saliva samples and different histological stages from morphologically normal epithelial tissues to dysplasia and EBVaGCs. We compared the genomic landscape between EBVaGCs and their precursor lesions and traced the clonal evolution for each patient. We also analyzed genome sequences of EBV from samples of different histological types. Finally, the key molecular events promoting the tumor evolution were demonstrated by MTT, IC50, and colony formation assay in vitro experiments and in vivo xenograft experiments.

resultsOur analysis revealed increasing mutational burden and EBV load from normal tissues and low-grade dysplasia (LD) to high-grade dysplasia (HD) and EBVaGCs, and oncogenic amplifications occurred late in EBVaGCs. Interestingly, within each patient, EBVaGCs and HDs were monoclonal and harbored single-strain-originated EBV, but saliva or normal tissues/LDs had different EBV strains from that in EBVaGCs. Compared with precursor lesions, tumor cells showed incremental methylation in promotor regions, whereas EBV presented consistent hypermethylation. Dominant alterations targeting the PI3K-Akt and Wnt pathways were found in EBV-infected cells. The combinational inhibition of these two pathways in EBV-positive tumor cells confirmed their synergistic function.

conclusionsWe portrayed the (epi) genomic evolution process of EBVaGCs, revealed the extensive genomic diversity of EBV between tumors and normal tissue sites, and demonstrated the synergistic activation of the PI3K and Wnt pathways in EBVaGCs, offering a new potential treatment strategy for this disease.

Indexed as

GenomicsAnimalsCarcinomaCell Line, TumorDNA MethylationEpstein-Barr Virus InfectionsFemaleGene Expression Regulation, NeoplasticHerpesvirus 4, HumanHumansMiceMice, Inbred BALB CMice, NudeMutationOncogenesPhosphatidylinositol 3-KinasesPhosphatidylinositol 3-Kinases

Identifiers

PMID34493320
PMCPMC8422682
OpenAlexW3198181673

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.