Is EBV found in cancer tissues involved in the formation of unknown cancer subtypes?

• Project/Area Number: 18K07284
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: OBOKI Keisuke 公益財団法人東京都医学総合研究所, ゲノム医学研究センター, 副参事研究員 (80415108)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: EBウイルス / 胃がん / EBV / ヒトヘルペスウイルス / 次世代シークエンシング / がん

Outline of Final Research Achievements

The prognosis of EBV-associated gastric cancer (EBVaGC) is still controversial.
In the TCGA-gastric cancer project, EBV molecular subtypes were combined with multiple next-generation sequencing (NGS) methods, but questions remain about the consistency of EBV positivity rates detected by different approaches. Therefore, we reanalyzed a public RNA sequencing dataset containing 375 tumor and 32 normal samples to define a reliable threshold for EBV reads. The prognostic impact of EBV on pathological subtypes was also analyzed. EBV-positive cases identified by the reanalysis were independent of infiltrating lymphocyte signatures and accounted for almost half of all cases, with longer overall survival in adenocarcinoma, NOS, and longer overall survival in tubular Adenocarcinoma and NOS, and shorter in Tubular adenocarcinoma.

Academic Significance and Societal Importance of the Research Achievements

EBウイルスががん細胞中に認められる胃がんサブタイプが知られる。これまで、EBVに由来するRNAが非常に多い場合のみが注目されてきたが、EBVは170000塩基を超えるゲノムを有し、そこに多くの遺伝子を有していて、その転写は一様では無い可能性がある。そのため、大量のRNA分子を解析することで、ごく微量のEBV RNAを検出し、これが新しい胃がんの予後予測因子となる可能性を示唆できた。

Research Products

• [Journal Article] Potential prognostic impact of EBV RNA-seq reads in gastric cancer: a reanalysis of The Cancer Genome Atlas cohort (2020)
  • Author(s): Sadato D, Ogawa M, Hirama C, Hishima T, Horiguchi S, Harada Y, Shimoyama T, Itokawa M, Ohashi K, Oboki K
  • Journal Title: FEBS Open Bio Volume: 10 Issue: 3 Pages: 455-467
  • DOI: 10.1002/2211-5463.12803
  • Peer Reviewed / Open Access
• [Journal Article] Distinct gene expression profiles and regulation networks of nasal polyps in eosinophilic and non-eosinophilic chronic rhinosinusitis. (2018)
  • Author(s): Okada N, Nakayama T, Asaka D, Inoue N, Tsurumoto T, Takaishi S, Otori N, Kojima H, Matsuda A, Oboki K, Saito H, Matsumoto K, Yoshikawa M.
  • Journal Title: Int Forum Allergy Rhinol. Volume: 8 Issue: 5 Pages: 592-604
  • DOI: 10.1002/alr.22083
  • Peer Reviewed
• [Journal Article] Eukaryotic translation initiation factor 3 (eIF3) subunit e is essential for embryonic development and cell proliferation. (2018)
  • Author(s): Sadato D, Ono T, Gotoh-Saito S, Kajiwara N, Nomura N, Ukaji M, Yang L, Sakimura K, Tajima Y, Oboki K, Shibasaki F.
  • Journal Title: FEBS Open Bio. Volume: 8 Issue: 8 Pages: 1188-1201
  • DOI: 10.1002/2211-5463.12482
  • Peer Reviewed / Open Access
• [Presentation] 胃がんサブタイプにおけるEBV陽性胃がん予後への異なる影響：TCGA RNA‐Seqデータセットの再分析 (2019)
  • Author(s): 貞任大地、大保木啓介、原田結花、堀口慎一郎、平間千津子、小川美奈、下山達
  • Organizer: 第78回日本癌学会学術集会
• [Presentation] 胃がんサブタイプにおけるEBV陽性胃がん予後への異なる影響：TCGA RNA‐Seqデータセットの再分析 (2019)
  • Author(s): 貞任大地、小川美奈、平間千津子、比島恒和、堀口純一郞、原田結花、下山達、大橋一輝、糸川昌成、大保木啓介
  • Organizer: 第42回日本分子生物学会学術集会