肺癌・食道癌の迅速病態診断系の構築:未病・早期癌検出と悪性度

2011 Fiscal Year Annual Research Report

• Project/Area Number: 21390178
• Research Institution: Shiga University of Medical Science
• Principal Investigator: 醍醐 弥太郎 滋賀医科大学, 医学部, 特任教授 (30345029)
• Keywords: 病態診断 / 個別化医療

Research Abstract

肺癌・食道癌の発症初期での検出および疾患増悪を早期に感知する統合的病態診断系を開発し、それを迅速に癌予防・診断・治療へ展開することを目的として、平成23年度は、バイオマーカー候補分子の同定を進めるとともに、複数のバイオマーカーを統合した新規診断システムの構築を行った。
(1)ELISA法等を用いた肺癌・食道癌の迅速血清診断系の構築
血清バイオマーカー候補に対する抗体を用いたELISA法による肺癌の早期血清診断システムの構築を行い、あらたに新規血清診断マーカーとしてEBI3を同定した。さらに複数のマーカーを組み合わせて、最小のマーカー数で最大の感度・特異度を示す診断系を検討した。糖鎖プロテオミクス解析と血清ペプチドーム解析による肺癌患者血清中のタンパクを探索して複数の候補バイオマーカーを同定した。
(2)免疫組織学的マーカーによる肺癌・食道癌の迅速悪性度診断法の構築
組織染色マーカーについて腫瘍組織マイクロアレイ(肺、食道癌他)および正常組織マイクロアレイを使用し免疫組織染色を行い、蛋白発現レベルと臨床病理・予後情報との相関を検討し、あらたに予後予測マーカーとして、CSTF2、CHODL、OIP5、CDC20、KIAA0101、MAD2、MCM7、EZH2を同定した。さらに最小のマーカー数で定量的に癌の悪性度を予測する診断法を検討した。
(3)肺癌・食道癌の迅速病態診断系の構築と検証
上記の血清および免疫組織学的マーカーを各診断段階で有機的に使い分ける肺癌・食道癌の迅速病態診断系を検討した。

Research Products

• [Journal Article] Characterization of an Opa interacting protein 5 involved in lung and esophageal carcinogenesis (2012)
  • Author(s): Koinuma J, Akiyama H, Fujita M, Hosokawa M, Tsuchiya E, Kondo S, Nakamura Y, Daigo Y
  • Journal Title: Cancer Sci Volume: 103 Pages: 577-586
  • DOI: 10.1111/j.1349-7006.2011.02167.x
  • Peer Reviewed
• [Journal Article] Overexpression of CDC20 predicts poor prognosis in primary non-small cell lung cancer patients (2012)
  • Author(s): Kato T, Daigo Y, Aragaki M, Ishikawa K, Sato M, Kaji M
  • Journal Title: J Surg Oncol Volume: (in press)
  • DOI: 10.1002/jso.23109
  • Peer Reviewed
• [Journal Article] Histone lysine methyltransferase Wolf-Hirschhorn syndrome candidate 1 is involved in human carcinogenesis through regulation of the Wnt pathway (2011)
  • Author(s): Toyokawa G, Cho HS, Masuda K, Yamane Y, Yoshimatsu M, Hayami S, Takawa M, Iwai Y, Daigo Y, Tsuchiya E, Tsunoda T, Field HI, Kelly JD, Neal DE, Maehara Y, Ponder BA, Nakamura Y, Hamamoto R
  • Journal Title: Neoplasia Volume: 13 Pages: 887-898
  • Peer Reviewed
• [Journal Article] The JmjC domain-containing histone demethylase KDM3A is a positive regulator of the G(1)/S transition in cancer cells via transcriptional regulation of the HOXA1 gene (2011)
  • Author(s): Cho HS, Toyokawa G, Daigo Y, Hayami S, Masuda K, Ikawa N, Yamane Y, Maejima K, Tsunoda T, Field HI, Kelly JD, Neal DE, Ponder BA, Maehara Y, Nakamura Y, Hamamoto R
  • Journal Title: Int J Cancer Volume: (in press)
  • DOI: 10.1002/ijc.26501
  • Peer Reviewed
• [Journal Article] Chondrolectin is a novel diagnostic biomarker and a therapeutic target for lung cancer (2011)
  • Author(s): Masuda K, Takano A, Oshita H, Akiyama H, Tsuchiya E, Kohno N, Nakamura Y, Daigo Y
  • Journal Title: Clin Cancer Res Volume: 17 Pages: 7712-7722
  • Peer Reviewed
• [Journal Article] Identification of Epstein-Barr Virus-Induced Gene 3 as a Novel Serum and Tissue Biomarker and a Therapeutic Target for Lung Cancer (2011)
  • Author(s): Nishino R, Takano A, Oshita H, Ishikawa N, Akiyama H, Ito H, Nakayama H, Miyagi Y, Tsuchiya E, Kohno N, Nakamura Y, Daigo Y
  • Journal Title: Clin Cancer Res Volume: 7 Pages: 6272-6286
  • Peer Reviewed
• [Journal Article] Characterization of a Cleavage Stimulation Factor, 3' pre-RNA, Subunit 2, 64kDa (CSTF2) as a Therapeutic Target for Lung Cancer (2011)
  • Author(s): Aragaki M, Takahashi K, Akiyama H, Tsuchiya E, Kondo S, Nakamura Y, Daigo Y
  • Journal Title: Clin Cancer Res Volume: 7 Pages: 5889-5900
  • Peer Reviewed
• [Journal Article] Overexpression of KIAA0101 predicts poor prognosis in primary lung cancer patients (2011)
  • Author(s): Kato T, Daigo Y, Aragaki M, Ishikawa K, Sato M, Kaji M
  • Journal Title: Lung Cancer Volume: (in press)
  • Peer Reviewed
• [Journal Article] Minichromosome Maintenance Protein 7 is a potential therapeutic target in human cancer and a novel prognostic marker of non-small cell lung cancer (2011)
  • Author(s): Toyokawa G, Masuda K, Daigo Y, Cho HS, Yoshimatsu M, Takawa M, Hayami S, Maejima K, Chino M, Field HI, Neal DE, Tsuchiya E, Ponder BA, Maehara Y, Nakamura Y, Hamamoto R
  • Journal Title: Mol Cancer Volume: 10 Pages: 65
  • Peer Reviewed
• [Journal Article] Validation of the histone hethyltransferase EZH2 as a therapeutic target for various types of human cancer and as a prognostic marker (2011)
  • Author(s): Takawa M, Masuda K, Kunizaki M, Daigo Y, Takagi K, Iwai Y, Cho HS, Toyokawa G, Yamane Y, Maejima K, Field HI, Kobayashi T, Akasu T, Sugiyama M, Tsuchiya E, Atomi Y, Ponder BA, Nakamura Y, Hamamoto R
  • Journal Title: Cancer Sci Volume: 102 Pages: 1298-1305
  • DOI: 10.1111/j.1349-7006.2011.01958.x
  • Peer Reviewed
• [Journal Article] A comprehensive peptidome profiling technology for the identification of early detection biomarkers for lung adenocarcinoma (2011)
  • Author(s): Ueda K, Saichi N, Takami S, Kang D, Toyama A, Daigo Y, Ishikawa N, Kohno N, Tamura K, Shuin T, Nakayama M, Sato TA, Nakamura Y, Nakagawa H
  • Journal Title: PLoS One Volume: 6 Pages: e18567
  • Peer Reviewed
• [Journal Article] Deglycosylation and label-free quantitative LC-MALDI MS applied to efficient serum biomarker discovery of lung cancer (2011)
  • Author(s): Toyama A, Nakagawa H, Natsuda K, Ishikawa N, Kohno N, Daigo Y, Sato TA, Nakamura Y, Ueda K
  • Journal Title: Proteome Sci Volume: 9 Pages: 18
  • Peer Reviewed
• [Journal Article] Overexpression of MAD2 predicts clinical outcome in primary lung cancer patients (2011)
  • Author(s): Kato T, Daigo Y, Aragaki M, Ishikawa K, Sato M, Kondo S, Kaji M
  • Journal Title: Lung Cancer Volume: 74 Pages: 24-131
  • Peer Reviewed
• [Journal Article] A novel tumor-associated antigen, cell division cycle 45-like can induce cytotoxic T-lymphocytes reactive to tumor cells (2011)
  • Author(s): Tomita Y, Imai K, Senju S, Irie A, Inoue M, Hayashida Y, Shiraishi K, Mori T, Daigo Y, Tsunoda T, Ito T, Nomori H, Nakamura Y, Kohrogi H, Nishimura Y
  • Journal Title: Cancer Sci Volume: 102 Pages: 697-705
  • DOI: 10.1111/j.1349-7006.2011.01865.x
  • Peer Reviewed
• [Presentation] Genome-wide association study of lung cancer : Association of variation in TP63 with lung adenocarcinoma susceptibility (2011)
  • Author(s): Yataro Daigo, Daiki Miki, Michiaki Kubo, Tatsuhiko Tsunoda, Naoyuki Kamatani, Kazuaki Chayama, Takashi Takahashi, Johji Inazawa, Yusuke Nakamura
  • Organizer: 第56回人類遺伝学会大会
  • Place of Presentation: 幕張
  • Year and Date: 2011-11-11
• [Presentation] VARIATION IN TP63 GENE CONFERS THE RISK OF LUNG ADENOCARCINOMA INTHE EAST ASIAN POPULATION (2011)
  • Author(s): Yataro Daigo, Yusuke Nakamura
  • Organizer: THE U.S.-JAPAN COOPERATIVE CANCER RESEARCH PROGRAM WORKSHOP : Cancer Genomics and Epigenomics : Towards personalized cancer medicine
  • Place of Presentation: Kyoto, Japan(招待講演)
  • Year and Date: 2011-10-25
• [Presentation] Genome-wide association study of lung cancer : Association of variation in TP63 with lung adenocarcinoma susceptibility (2011)
  • Author(s): Yataro Daigo, Yusuke Nakamura
  • Organizer: 第70回日本癌学会総会
  • Place of Presentation: 名古屋(招待講演)
  • Year and Date: 2011-10-01
• [Presentation] From Cancer Genomics to Medical Oncology : Novel Biomarker and Therapeutic Target Discovery for Lung and Esophageal Cancer (2011)
  • Author(s): Yataro Daigo, Yusuke Nakamura
  • Organizer: Japanese-German Cancer Workshop
  • Place of Presentation: Hiroshima, Japan(招待講演)
  • Year and Date: 2011-09-19
• [Presentation] Identification of a novel oncoprotein CDCA5 as a biomarker and a molecular target for cell-permeable peptide/small molecule-based drugs (2011)
  • Author(s): Yataro Daigo, Atsushi Takano, Minh Hue Nguyen, Yusuke Nakamura
  • Organizer: 第9回日本臨床腫瘍学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2011-07-23
• [Presentation] Discovery of oncoproteins as cancer biomarkers and molecular targets for antibody-based immunotherapy (2011)
  • Author(s): Yataro Daigo, Atsushi Takano, Yusuke Nakamura
  • Organizer: 2011 ASCO Annual meeting
  • Place of Presentation: Chicago, USA
  • Year and Date: 2011-06-05
• [Presentation] From Cancer Genomic to the Cancer Clinic : Novel Biomarker and Therapeutic Targecs Discovery for Lung and Esophageal Cancer (2011)
  • Author(s): Yataro Daigo, Yusuke Nakamura
  • Organizer: Cold Spring Harbor Asia Conference on Translational Approaches to Cancer
  • Place of Presentation: Suzhou, China(招待講演)
  • Year and Date: 2011-05-26
• [Presentation] Dickkopf-1 as a Biomarker and a Molecular Target for Antibody-based Cancer Immunotherapy (2011)
  • Author(s): Yataro Daigo, Nagato Sato, Atsushi Takano, Yusuke Nakamura
  • Organizer: 102nd AACR Annual meeting
  • Place of Presentation: Florida, USA
  • Year and Date: 2011-04-04
• [Book] カレントセラピー (2011)
  • Author(s): 醍醐弥太郎
  • Total Pages: 90
  • Publisher: ライフメディコム社
• [Book] がん治療レクチャー (2011)
  • Author(s): 高野淳、醍醐弥太郎
  • Total Pages: 450
  • Publisher: 総合医学社