Gastric Cancer

, Volume 21, Issue 6, pp 1064–1070 | Cite as

Transcriptional analysis of immune genes in Epstein–Barr virus-associated gastric cancer and association with clinical outcomes

  • Raghav Sundar
  • Aditi Qamra
  • Angie Lay Keng Tan
  • Shenli Zhang
  • Cedric Chuan Young Ng
  • Bin Tean Teh
  • Jeeyun Lee
  • Kyoung-Mee KimEmail author
  • Patrick TanEmail author
Short Communication



Epstein–Barr virus-associated gastric cancer (EBVaGC) has traditionally been associated with high expression of PD-L1 and immune infiltration. Correlations between PD-L1 and other immune-related gene (IRG) expressions in EBVaGC have not been previously described.


We performed NanoString® transcriptomic profiling and PD-L1 immunohistochemistry (IHC) (using the FDA approved Dako PD-L1 IHC 22C3) on EBVaGC samples from gastric cancer patients undergoing primary tumor resections at Samsung Medical Centre, South Korea. For controls, EBV-negative samples from the previously reported Asian Cancer Research Group (EBVnegACRG) cohort were used. Genes tested included PD-L1 and other IRGs related to intra-tumoral cytolytic activity, cytokines and immune checkpoints. Samples with PD-L1 expression > 34th percentile were defined as PD-L1high and the remaining as PD-L1low.


We identified 71 cases of EBVaGC and 193 EBV-negative ACRG samples as controls. EBVaGC showed higher expression of all queried immune genes compared to EBVnegACRG samples (p < 0.01). PD-L1 immunohistochemistry expression correlated with PD-L1 transcript expression (r = 0.63, p < 0.001). Tumor-infiltrating lymphocyte patterns were also found to be different between PD-L1low and PD-L1high groups. PD-L1low EBVaGC samples (n = 24, 34%) had consistently decreased expression of all other immune genes, such as CD8A, GZMA and PRF1 and PD-1 (p < 0.001). PD-L1low EBVaGC samples were also associated with worse disease-free survival (HR 5.03, p = 0.032) compared to PD-L1high EBVaGC samples.


A substantial proportion of EBVaGC does not express high levels of PD-L1 and other immune genes. EBVaGCs which have lower transcriptomic expression of PD-L1 tend to have a similarly low expression of other immune genes, IHC scores and a poorer prognosis.


Epstein–Barr virus-associated gastric cancer Immune genes PD-L1 



RS is supported by a National Medical Research Council (NMRC) MOH Healthcare Research Scholarship, Singapore. PT is supported by Duke-NUS Medical School and the Biomedical Research Council, Agency for Science, Technology and Research. JL and KKM are supported by a Grant from the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI16C1990). This work was also supported by National Medical Research Council Grants TCR/009-NUHS/2013 and NMRC/STaR/0026/2015. This work was also provided by Korea National Research Foundation (NRF-2017R1D1A1B03032449).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Ethical standards

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent to be included in the study, or the equivalent, was obtained from all patients.

Supplementary material

10120_2018_851_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 14 KB)
10120_2018_851_MOESM2_ESM.pdf (137 kb)
Supplementary Figure 1. KM survival curves of PD-L1high and PD-L1low samples after excluding samples older than 10 years (1996-2006) (PDF 136 KB)
10120_2018_851_MOESM3_ESM.pdf (120 kb)
Supplementary Figure 2. Scatter plot showing correlation between PD-L1 IHC CPS score (log-scale) and PD-L1 RNA transcript expression levels (log-scale) (PDF 120 KB)
10120_2018_851_MOESM4_ESM.docx (12 kb)
Supplementary material 4 (DOCX 12 KB)


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Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2018

Authors and Affiliations

  • Raghav Sundar
    • 1
    • 2
  • Aditi Qamra
    • 2
  • Angie Lay Keng Tan
    • 2
  • Shenli Zhang
    • 2
  • Cedric Chuan Young Ng
    • 4
  • Bin Tean Teh
    • 4
  • Jeeyun Lee
    • 5
  • Kyoung-Mee Kim
    • 6
    Email author
  • Patrick Tan
    • 2
    • 3
    • 7
    • 8
    Email author
  1. 1.Department of Haematology-OncologyNational University Health SystemSingaporeSingapore
  2. 2.Cancer and Stem Cell Biology ProgramDuke-NUS Medical SchoolSingaporeSingapore
  3. 3.Biomedical Research CouncilAgency for Science, Technology and ResearchSingaporeSingapore
  4. 4.Laboratory of Cancer Epigenome, Department of Medical SciencesNational Cancer CentreSingaporeSingapore
  5. 5.Division of Hematology/Oncology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea
  6. 6.Department of Pathology and Translational Genomics, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea
  7. 7.Cancer Science Institute of SingaporeNational University of SingaporeSingaporeSingapore
  8. 8.SingHealth/Duke-NUS Institute of Precision MedicineNational Heart Centre SingaporeSingaporeSingapore

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