Pan-cancer multi-omics analysis toward identification of novel diagnostic and therapeutic target molecules in neuroendocrine tumors

• Project/Area Number: 18K07343
• 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: Shizuoka Cancer Center Research Institute
• Principal Investigator: Ohshima Keiichi 静岡県立静岡がんセンター(研究所), その他部局等, 研究員 (10399587)
• 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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 神経内分泌腫瘍 / 腫瘍マーカー / ドライバー遺伝子 / オミックス解析

Outline of Final Research Achievements

Neuroendocrine tumors (NETs) are rare tumors that are found in all organs and account for 1-2% of all tumors, but the incidence is increasing every year. In particular, non-functional NETs without hormone-producing symptoms progress without specific symptoms, and are detected only after enlargement or distant metastasis. In addition, NSE and chromogranin A, which are diagnostic markers in blood, have problems in sensitivity and specificity, so that imaging diagnosis is currently the main method. In this study, we analyzed multi-omics data, including gene mutation and copy number data from whole exome analysis and comprehensive gene expression data, in 90 cases of NETs arising in the gastrointestinal tract and lungs. Among the genes commonly expressed in NETs across organs, we targeted a gene-derived protein as a NET blood marker, and prepared its region-specific antisera. We hope that these antibodies are useful to develop a new blood-based diagnostic NET marker.

Academic Significance and Societal Importance of the Research Achievements

NETは全臓器的に認められ、全腫瘍の1～2%を占める稀な腫瘍であるが、罹患率は年々上昇傾向にある。特にホルモン産生症状のない非機能性NETは特異的症状がなく進行するため、増大後や遠隔転移後にはじめて発見される。また、血中診断マーカーのNSEやクロモグラニンAは感度や特異度に問題点があるため、現状は画像診断が中心となる。本成果は、こうしたNET血中診断に向けた新しい腫瘍マーカー候補として期待される。

Research Products

• [Journal Article] Japanese version of The Cancer Genome Atlas, JCGA, established using fresh frozen tumors obtained from 5143 cancer patients. (2020)
  • Author(s): Nagashima T, Yamaguchi K, Terashima M, et al.
  • Journal Title: Cancer Science Volume: 111 Issue: 2 Pages: 687-699
  • DOI: 10.1111/cas.14290
  • Peer Reviewed / Open Access
• [Presentation] Analysis of somatic and germline mutations of MEN1 in 5,063 cancer patients. (2020)
  • Author(s): Akane Naruoka, Sumiko Ohnami, Takeshi Nagashima, Keiichi Ohshima, Masakuni Serizawa, Keiichi Hatakeyama, Shumpei Ohnami, Yasue Horiuchi, Kenichi Urakami, Yasuto Akiyama, Ken Yamaguchi
  • Organizer: The 79th Annual Meeting of the Japanese Cancer Association
• [Presentation] Potential drug-targetable driver oncogenes resulting from amplification and overexpression in 4,000 solid tumors (2018)
  • Author(s): Keiichi Ohshima, Takeshi Nagashima, Keiichi Hatakeyama, Sumiko Ohnami, Shumpei Ohnami, Yuji Shimoda, Tomoe Tanabe, Masakuni Serizawa, Yasuto Akiyama, Kenichi Urakami, Masatoshi Kusuhara, Tohru Mochizuki, Ken Yamaguchi
  • Organizer: 第77回日本癌学会学術総会