Identification of gene expression and abnormalities that define clinicopathological features of biliary tract carcinoma and their application in diagnosis and treatment

• Project/Area Number: 17K08769
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Keio University
• Principal Investigator: Ojima Hidenori 慶應義塾大学, 医学部(信濃町), 准教授 (80342905)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); 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); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 胆道領域がん / 細胞株 / 細胆管細胞癌 / 分子病理学的 / 遺伝子変異 / GSEA / 胆道領遺伝子発現 / 血管新生 / 放射線感受性 / 遺伝子発現 / 新鮮切除検体 / データベース

Outline of Final Research Achievements

We investigated the molecular pathological significance of cholangiolocellular carcinoma (CoCC). We analyzed the differences in gene expression of cholangiocellular carcinoma (CCC), with and without CoCC, using gene set enrichment analysis as well as gene abnormalities using a whole-exome sequence database. Thus, a group of CCC with CoCC, in comparison with CCC without CoCC, was found to be significantly associated with genes involved in favorable prognosis, inflammatory response, and angiogenesis; in contrast, the gene abnormalities of cancer-related genes, such as the typical TP53, were significantly low. These results are consistent with the clinicopathological feature of CoCC.

Academic Significance and Societal Importance of the Research Achievements

形態学から導かれる胆道領域がんの生物学的特性に関わる臨床病理学的特徴を有する腫瘍として、細胆管細胞癌を選び分子病理学的手法を用いた解析を行なった。その結果、形態学的と臨床病理学的な関連が、分子病理学的にも裏付けされることが示された。本研究から導き出された機能分子や機能解析結果は、不明な点が多い胆道領域がんの腫瘍増殖・進展機構の一端を明らかにしただけでなく、将来の治療戦略や治療評価への応用の可能性を示唆する結果となった。

Research Products

• [Journal Article] Synergistic and Pharmacotherapeutic Effects of Gemcitabine and Cisplatin Combined Administration on Biliary Tract Cancer Cell Lines (2019)
  • Author(s): Sakamoto Yasunari、Yamagishi Seri、Okusaka Takuji、Ojima Hidenori
  • Journal Title: Cells Volume: 8 Issue: 9 Pages: 1026-1026
  • DOI: 10.3390/cells8091026
  • Peer Reviewed
• [Journal Article] PI3K-mTOR pathway identified as a potential therapeutic target in biliary tract cancer using a newly established patient-derived cell panel assay (2018)
  • Author(s): Sakamoto Y., Yamagishi S., Tanizawa Y., Tajimi M., Okusaka T., Ojima H
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 48 Issue: 4 Pages: 396-399
  • DOI: 10.1093/jjco/hyy011
  • Peer Reviewed / Open Access
• [Journal Article] 肝胆膵領域に対する病理学的治療効果判定 (2017)
  • Author(s): 尾島英知, 益田悠貴, 前原純樹, 上野彰久, 坂本康成
  • Journal Title: 病理と臨床 Volume: 35 Pages: 1002-1009
• [Presentation] Gamma-Synuclein is a novel prognostic marker and promotes tumor cell migration in biliary tract carcinoma. (2020)
  • Author(s): Yusuke Takemura, Hidenori Ojima, Go Oshima, Naoto Kubota, Masahiro Shinoda, Minoru Kitago, Hiroshi Yagi, Yuta Abe, Shutaro Hori, Yuki Masuda, Yoko Nishimura, Taizo Hibi, Michiie Sakamoto, Yuko Kitagawa
  • Organizer: Gastrointestinal Cancers Symposium 2020
  • Int'l Joint Research
• [Presentation] 病理形態学を基盤とした、胆道悪性腫瘍の進展に関わる分子機構の解明 (2019)
  • Author(s): 尾島英知
  • Organizer: 第65回 日本病理学会秋期特別総会 (学術研究賞演説)
  • Invited
• [Presentation] SYNERGISTIC EFFECTS AND PHARMACOTHERAPEUTIC ACTIVITY OF GEMCITABINE AND CISPLATIN COMBINATION THERAPY IN BILIARY TRACT CANCER CELL LINES (2019)
  • Author(s): Yasunari Sakamoto, Seri Yamagishi, Takuji Okusaka, Hidenori Ojima.
  • Organizer: United European Gastroenterology Week 2019
  • Int'l Joint Research
• [Presentation] 肝腫瘍の病理と臨床、その基本事項と未来像. ～NASHや糖尿病との関連も含めて～ (2018)
  • Author(s): 尾島英知
  • Organizer: 日本超音波医学会第48回北海道地方会学術集会
  • Invited