ArticlePloS one2019
Viral loads correlate with upregulation of PD-L1 and worse patient prognosis in Epstein-Barr Virus-associated gastric carcinoma.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Global Epidemiology of PD-L1 Expression in Epstein-Barr Virus-Associated Gastric Cancer: A Systematic Review and Meta-Analysis.Journal of gastrointestinal cancer · 2025Pooled it
- EBV Early Lytic Antigens, EBNA2 and PDL-1, in Progressive Multiple Sclerosis Brain: A Coordinated Contribution to Viral Immune Evasion.International journal of molecular sciences · 2025Article
- Gastrointestinal inflammation and cancer: viral and bacterial interplay.Gut microbes · 2025Review
- Article
- Recent advances in the mechanisms of PD-L1 expression in gastric cancer: a review.Biological research · 2025Review
- Transcriptional and microbial profile of gastric cancer patients infected with Epstein-Barr virus.Frontiers in oncology · 2025Article
- Prognostic role ofHeliyon · 2024Article
- Predictive Biomarkers for Immunotherapy in Gastric Cancer: Current Status and Emerging Prospects.International journal of molecular sciences · 2023Review
- Role of Exosomes and Their Potential as Biomarkers in Epstein-Barr Virus-Associated Gastric Cancer.Cancers · 2023Review
- Mechanisms of T cell evasion by Epstein-Barr virus and implications for tumor survival.Frontiers in immunology · 2023Review
- EBV and HPV Infections in Colorectal Cancer and Their Effect on P53 and P16 Protein Expression.International journal of molecular and cellular medicine · 2023Article
- Epstein-barr virus/Iranian journal of microbiology · 2022Article
- Signaling pathways and therapeutic interventions in gastric cancer.Signal transduction and targeted therapy · 2022Review
- Checkpoint CD47 expression in classical Hodgkin lymphoma.British journal of haematology · 2022Article
- PD-L1 expression in EBV associated gastric cancer: a systematic review and meta-analysis.Discover oncology · 2022Review
- The Epstein-Barr Virus Hacks Immune Checkpoints: Evidence and Consequences for Lymphoproliferative Disorders and Cancers.Biomolecules · 2022Review
- Viral and cellular oncogenes promote immune evasion.Oncogene · 2022Review
- Article
- Review
- Clinicopathological features of tumor mutation burden, Epstein-Barr virus infection, microsatellite instability and PD-L1 status in Chinese patients with gastric cancer.Diagnostic pathology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC), one of four major gastric cancer types, consists of clonal growth of EBV-infected epithelial cells. However, the significance of viral loads in each tumor cell has not been evaluated. EBV-DNA is stably maintained in episomal form in the nucleus of each cancer cell. To estimate EBV copy number per genome (EBV-CN), qPCR of viral EBNA1 and host GAPDH, standardized by Namalwa DNA (one copy/genome), was applied to the formalin-fixed paraffin embedded (FFPE) surgically resected EBVaGC specimens (n = 43) and EBVaGC cell lines (SNU-719 and NCC-24). In surgical specimens, the cancer cell ratio (CCR) was determined with image analysis, and EBV-CN was obtained by adjusting qPCR value with CCR. Fluorescent in situ hybridization (FISH) was also applied to the FFPE sections using the whole EBV-genome as a probe. In surgical specimens, EBV-CN obtained by qPCR/CCR was between 1.2 and 185 copies with a median of 9.9. EBV-CN of SNU-719 and NCC-24 was 42.0 and 1.1, respectively. A linear correlation was observed with qPCR/CCR data up to 20 copies/genome (40 signals/nucleus), the limit of FISH analysis. In addition, substantial variation in the number of EBV foci was observed. Based on qPCR/CCR, high EBV-CN (>10 copies) correlated with PD-L1 expression in cancer cells (P = 0.015), but not with other pathological indicators. Furthermore, EBVaGC with high EBV-CN showed worse disease-specific survival (P = 0.041). Our findings suggest that cancer cell viral loads may contribute to expression of the immune checkpoint molecule and promotion of cancer progression in EBVaGC.
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