Identification of new biomarkers and therapeutic targets for lung cancer

• Project/Area Number: 24501341
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnosis
• Research Institution: The University of Tokyo (2014); Shiga University of Medical Science (2012-2013)
• Principal Investigator: ATSUSHI TAKANO 東京大学, 医科学研究所, 特任講師 (50582607)
• Co-Investigator(Kenkyū-buntansha): DAIGO Yataro 滋賀医科大学, 医学部, 教授 (30325029) ; 醍醐 弥太郎 滋賀医科大学, 医学部, 教授 (30345029)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: バイオマーカー / 治療標的分子 / 国際情報交換 / アメリカ

Outline of Final Research Achievements

We identified a secreted proteins, LASEP1 and LASEP3 (LASEPs) as a candidate. Immunohistochemical staining showed that high level of LASEPs expression was associated with poor prognosis for NSCLC patients. Serum LASEPs levels were higher in NSCLC patients than in healthy volunteers. Furthermore, reduction of LASEPs by siRNA suppressed lung cancer cell proliferation and induced apoptosis. In addition, subsequent microarray analysis of these cancer cells identified several candidate downstream genes of LASEPs that relate to cell growth signals.
Next generation sequencer analysis detected tumor-specific mutation in lung cancer tissue. In addition, we detected mutation in mRNA from serum exosome or free DNA from serum by digital PCR. Digital PCR analysis showed that activating EGFR mutation in serum exosome was detected 4 cases out of 10.

Research Products

• [Journal Article] Cell division cycle-associated protein 1 overexpression is essential for the malignant potential of colorectal cancers. (2014)
  • Author(s): Kobayashi Y, Takano A, Miyagi Y, Tsuchiya E, Sonoda H, Shimizu T, Okabe H, Tani T, Fujiyama Y, Daigo Y.
  • Journal Title: International journal of oncology Volume: 44 Issue: 1 Pages: 69-77
  • DOI: 10.3892/ijo.2013.2177
  • Peer Reviewed
• [Journal Article] A Systematic Approach to the Development of Novel Therapeutics for Lung Cancer using Genomic Analyses. (2013)
  • Author(s): Daigo Y, Takano A, Teramoto K, Chung S, Nakamura Y.
  • Journal Title: Clin Pharmacol Ther Volume: 94 Issue: 2 Pages: 218-223
  • DOI: 10.1038/clpt.2013.90
  • Peer Reviewed
• [Journal Article] RASEF is a novel diagnostic biomarker and a therapeutic target for lung cancer. (2013)
  • Author(s): Oshita H, Nishino R, Takano A, Fujitomo T, Aragaki M, Kato T, Akiyama H, Tsuchiya E, Kohno N, Nakamura Y, Daigo Y.
  • Journal Title: Molecular Cancer Research Volume: Epub ahead of print Pages: 0-0
  • Peer Reviewed
• [Presentation] 肺癌の新規診断マーカー、予後マーカー、治療標的分子であるLASEP1の機能解析 (2014)
  • Author(s): 高野淳、中村祐輔、醍醐弥太郎
  • Organizer: 第59回人類遺伝学会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-19 – 2014-11-22
• [Presentation] Characterization of LASEP3 as a serum diagnostic and prognostic biomarker and therapeutic target for lung cancer. (2014)
  • Author(s): Takano A, Nakamura Y, Daigo Y.
  • Organizer: 第73回日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] LASEP3 as a serological and prognostic biomarker and a therapeutic target (2014)
  • Author(s): Takano A, Nakamura Y, Daigo Y.
  • Organizer: 第12回日本臨床腫瘍学会
  • Place of Presentation: 福岡
  • Year and Date: 2014-07-17 – 2014-07-19
• [Presentation] Identification of a lung cancer growth factor, LASEP1 as a serological and prognostic biomarker and a therapeutic target (2014)
  • Author(s): Takano A, Nakamura Y, Daigo Y.
  • Organizer: 2014 ASCO annual meeting
  • Place of Presentation: シカゴ、米国
  • Year and Date: 2014-05-30 – 2014-06-03
• [Presentation] Characterization of LASEP3 as a serological and prognostic biomarker and a therapeutic target for lung cancer (2014)
  • Author(s): Takano A, Nakamura Y, Daigo Y.
  • Organizer: 2014 AACR annual meeting
  • Place of Presentation: サンディエゴ、米国
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] トランスクリプト―ム解析により同定した肺癌の新規バイオマーカーで治療標的分子であるLASEP3の機能解析 (2013)
  • Author(s): 高野淳、中村祐輔、醍醐弥太郎
  • Organizer: 第58回人類遺伝学会大会
  • Place of Presentation: 仙台
• [Presentation] Characterization of LASEP1 as a serological and prognostic biomarker and a therapeutic target for lung cancer (2013)
  • Author(s): 高野淳、中村祐輔、醍醐弥太郎
  • Organizer: 第72回日本癌学会
  • Place of Presentation: 横浜
• [Presentation] Characterization of a lung cancer growth factor, LASEP3 as a serological and prognostic biomarker and therapeutic target (2013)
  • Author(s): 高野淳、中村祐輔、醍醐弥太郎
  • Organizer: 第11回臨床腫瘍学会
  • Place of Presentation: 仙台
• [Presentation] Identification of LASEP3 as a new serological and prognostic biomarker for lung cancer. (2013)
  • Author(s): 高野淳、中村祐輔、醍醐弥太郎
  • Organizer: 2011 ASCO Annual meeting
  • Place of Presentation: Chicago, USA
• [Presentation] 大学病院におけるがん薬物療法レジメン審査委員会が果たす役割と今後の課題 (2013)
  • Author(s): 高野淳、醍醐弥太郎
  • Organizer: 第110回日本内科学会総会
  • Place of Presentation: 東京
• [Presentation] Characterization of a lung cancer growth factor, LASEP3 as a serological and prognostic biomarker and a therapeutic target (2013)
  • Author(s): 高野淳、中村祐輔、醍醐弥太郎
  • Organizer: 2013 AACR Annual meeting
  • Place of Presentation: Wachington, USA
• [Presentation] Characterization of a lung cancer growth factor, LASEP3 as a serological and prognostic biomarker and a therapeutic target (2013)
  • Author(s): 高野 淳、中村 祐輔、醍醐 弥太郎
  • Organizer: AACR annual meeting 2013
  • Place of Presentation: ワシントンDC、アメリカ合衆国
• [Presentation] Characterization of a lung cancer growth factor, LASEP1, as a serologic and prognostic biomarker and therapeutic target. (2013)
  • Author(s): 高野 淳、中村 祐輔、醍醐 弥太郎
  • Organizer: ASCO annual meeting 2013
  • Place of Presentation: シカゴ、アメリカ合衆国
• [Presentation] 包括的遺伝子解析に基づいた肺癌の新規診断マーカー・治療標的分子であるLASEP１の同定と機能解析 (2012)
  • Author(s): 高野 淳、中村 祐輔、醍醐 弥太郎
  • Organizer: 第56回人類遺伝学会
  • Place of Presentation: 京王プラザホテル
• [Presentation] Characterization of a lung cancer growth factor, LASEP1 as a serological and prognostic biomarker and a therapeutic target (2012)
  • Author(s): 高野 淳、中村 祐輔、醍醐 弥太郎
  • Organizer: 第10回日本臨床腫瘍学会
  • Place of Presentation: 大阪国際会議場
• [Presentation] Identification of LASEP3 as a diagnostic biomarker and therapeutic target for lung cancer (2012)
  • Author(s): 高野 淳、中村 祐輔、醍醐 弥太郎
  • Organizer: 第71回日本癌学会
  • Place of Presentation: ロイトン札幌
• [Presentation] Identification and analysis of a lung cancer growth factor, LASEP1 as a serological and prognostic biomarker and a therapeutic target (2012)
  • Author(s): 高野 淳、中村 祐輔、醍醐 弥太郎
  • Organizer: AACR annual meeting 2012
  • Place of Presentation: シカゴ、アメリカ合衆国
• [Presentation] Identification of LASEP3 as a new serological and prognostic biomarker for lung and various type of cancer (2012)
  • Author(s): 高野 淳、中村 祐輔、醍醐 弥太郎
  • Organizer: ASCO annual meeting 2012
  • Place of Presentation: シカゴ、アメリカ合衆国