Identification of novel biomarkers for non-small cell lung cancer

• Project/Area Number: 17K15009
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor diagnostics
• Research Institution: The University of Tokyo
• Principal Investigator: Noguchi Satoshi 東京大学, 医学部附属病院, 助教 (60732807)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 非小細胞肺癌 / バイオマーカー / 癌

Outline of Final Research Achievements

We explored novel biomarkers for non-small cell lung cancer using gene expression analysis technique, CAGE (Cap Analysis of Gene Expression). CRIP1, an actin cytoskeleton-interacting LIM-domain protein, was found to be involved in proliferation and colony formation of lung cancer cells. The analysis of a large cohort of non-small cell lung cancer (NSCLC) patients revealed that NSCLC patients with higher tumor CRIP1 expression levels tend to have an unfavorable prognosis.
In addition, the analysis of the TCGA database identified RhoV, which is a member of the Rho family of GTPases, to be involved in cancer metastasis. High expression of RhoV was associated with poor prognosis in lung adenocarcinoma patients. In vitro, knockdown of RhoV led to decreased cell proliferation and migration.

Academic Significance and Societal Importance of the Research Achievements

本研究では、理化学研究所により開発されたCAGE法による遺伝子発現解析やTCGAデータベースを用いた解析により、肺癌の進展や転移に関わる新規バイオマーカーであるCRIP1とRhoVを見出すことができた。いずれも正常気道/肺上皮と比較し一部の非小細胞肺癌に特異的に発現すること、高発現が予後不良因子となりえること、細胞増殖や遊走に寄与することが判明し、肺がんの新規治療標的になりうると考えられた。

Research Products

• [Journal Article] Active mTOR in Lung Epithelium Promotes Epithelial-Mesenchymal Transition and Enhances Lung Fibrosis (2020)
  • Author(s): Saito M, Mitani A, Ishimori T, Miyashita N, Isago H, Mikami Y, Noguchi S, Tarui M, Nagase T.
  • Journal Title: Am J Respir Cell Mol Biol Volume: - Issue: 6 Pages: 699-708
  • DOI: 10.1165/rcmb.2019-0255oc
  • Peer Reviewed / Open Access
• [Journal Article] CISH is a negative regulator of IL-13-induced CCL26 production in lung fibroblasts (2019)
  • Author(s): Takeshima Hideyuki、Horie Masafumi、Mikami Yu、Makita Kosuke、Miyashita Naoya、Matsuzaki Hirotaka、Noguchi Satoshi、Urushiyama Hirokazu、Hiraishi Yoshihisa、Mitani Akihisa、Borok Zea、Nagase Takahide、Yamauchi Yasuhiro
  • Journal Title: Allergology International Volume: 68 Issue: 1 Pages: 101-109
  • DOI: 10.1016/j.alit.2018.08.005
  • NAID: 130007557853
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Naftopidil reduced the proliferation of lung fibroblasts and bleomycin-induced lung fibrosis in mice. (2019)
  • Author(s): Urushiyama H, Terasaki Y, Nagasaka S, Kokuho N, Endo Y, Terasaki M, Kunugi S, Makita K, Isago H, Hosoki K, Souma K, Ishii T, Matsuzaki H, Hiraishi Y, Mikami Y, Noguchi S, Tamiya H, Mitani A, Yamauchi Y, Shimizu A, Nagase T.
  • Journal Title: J Cell Mol Med. Volume: 3 Issue: 5 Pages: 1-9
  • DOI: 10.1111/jcmm.14255
  • Peer Reviewed / Open Access