Exploration of a prognostic biomarker for lung cancer as personalized medicine using a genome-wide approach

• Project/Area Number: 21591001
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Saitama Medical University
• Principal Investigator: KOYAMA Nobuyuki 埼玉医科大学, 医学部, 講師 (30353460)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: EZH2 / 非小細胞肺癌 / 予後予測因子 / ゲノムワイド / 個別化医療 / H3K27 / ChIP-on-chip / Effector / CHIP-on-chip / 転移 / 浸潤 / siRNA / 予後診断マーカー

Research Abstract

Using immunohistochemistry for EZH2, we showed that the EZH2-expressing group reduced survival of stage I NSCLC compared with the non-EZH2-expressing group. In COX proportional hazard models, the non-EZH2-expressing group was independently associated with prolonged survival. These results suggest that EZH2 can be a novel predictive factor for prognosis in postsurgical NSCLC at stage I. Furthermore, using shRNA-mediated knockdown of EZH2 expression, in vitro cell growth assay and matrigel invasion assay showed that the suppression of EZH2 expression inhibited cellular proliferation and reduced invasion and metastatic potentials. Thus, EZH2 may function as an oncogene.

Research Products

• [Journal Article] Enhancer of Zeste Homolog 2 Is a Novel Prognostic Biomarker in Nons mall Cell Lung Cancer (2012)
  • Author(s): Huqun, Rinako Ishikawa, Jialing Zhang, Hitoshi Miyazawa, Yoshiya Goto, Yoshihiko Shimizu, Koichi Hagiwara, Nobuyuki Koyama
  • Journal Title: Cancer Volume: 118 Issue: 6 Pages: 1599-606
  • DOI: 10.1002/cncr.26441
  • Peer Reviewed
• [Journal Article] Enhancer of Zeste Homolog 2 Is a Novel Prognostic Biomarker in Nonsmall Cell Lung Cancer (2011)
  • Author(s): Huqun, Ishikawa R, Zhang J, Miyazawa H, Goto Y, Shimizu Y, Hagiwara K, and Koyama N
  • Journal Title: Cancer
  • Peer Reviewed
• [Journal Article] ^<18> F-fluorodeoxyglucose positron emission tomography for relapsing polychondritis as a diagnostic approach and evaluation of disease activity (2009)
  • Author(s): Yokoyama T, Koyama N, Kodama K, Hagiwara K, Kanazawa M
  • Journal Title: BMJ Case Reports
  • Peer Reviewed
• [Presentation] I期非小細胞肺癌に対する予後因子としてのEZH2 :発現と機能解析 (2011)
  • Author(s): 小山信之
  • Organizer: 第6回肺癌分子病態研究会
  • Place of Presentation: 東京
  • Year and Date: 2011-09-03
• [Presentation] I期非小細胞肺癌に対する予後因子としてのEZH2:発現と機能解析 (2011)
  • Author(s): 小山信之
  • Organizer: 第6回肺癌分子病態研究会
  • Place of Presentation: 東京、日本(招待講演)
  • Year and Date: 2011-09-03
• [Presentation] 当院における高齢者に対する気管支鏡検査の検討 (2011)
  • Author(s): 小山信之、嶺崎祥平、前野有理、山崎進、内田由佳、加賀亜希子、岡野哲也、村山芳武、小林国彦
  • Organizer: 第34回日本呼吸器内視鏡学会学術集会
  • Place of Presentation: 静岡
  • Year and Date: 2011-06-16
• [Presentation] EGFR gene mutation as a predicitive marker of the response to pemetrexed-based chemotherapy in non-small cell lung cancer (2011)
  • Author(s): Koyama N, Ishikawa R, Miyazawa H, Hagiwara K and Kobayashi K
  • Organizer: The 102st American Association for Cancer Research Annual Meeting 2011
  • Place of Presentation: オーランド, USA
  • Year and Date: 2011-04-02
• [Presentation] 非小細胞肺癌症例へのPemetrexed治療に対する臨床的検討 (2010)
  • Author(s): 小山信之、長井良昭、内田義孝、前野有理、嶺崎祥平、内田由佳、大谷秀雄、村山芳武、小林国彦
  • Organizer: 第51回日本肺癌学会総会
  • Place of Presentation: 広島
  • Year and Date: 2010-11-03
• [Presentation] 当院における再発・進行非小細胞肺癌症例に対するerlotinib治療の臨床的検討 (2010)
  • Author(s): 内田義孝、小山信之、小宮山謙一郎、嶺崎祥平、内田由佳、宮下起幸、前野有理、大谷秀雄、村山芳武、小林国彦
  • Organizer: 第51回日本肺癌学会総会
  • Place of Presentation: 広島
  • Year and Date: 2010-11-03
• [Presentation] HYAL2 promoter methylation analysis in malignant pleural mesothelioma (2010)
  • Author(s): Sadakata R, Miyazawa H, Jialing Z, Huqun, Gotoh Y, Shimizu Y, Kobayashi K, Ishikawa Y, Hagiwara K, and Koyama N
  • Organizer: 第68日本癌学会学術総会
  • Place of Presentation: 神奈川
  • Year and Date: 2010-10-01
• [Presentation] 悪性胸膜中皮腫におけるHYAL2 DNAプロモーター領域のメチル化解析 (2010)
  • Author(s): 小山信之、貞方里奈子、張嘉玲、呼群、後藤義也、清水禎彦、小林国彦、石川雄一、萩原弘一
  • Organizer: 第50回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2010-04-22
• [Presentation] Hypermethylation of semaphorin 3B promoter in malignant mesothlioma (2010)
  • Author(s): Koyama N, Zhang J, Sadakata R, Goto Y, Shimizu Y, Kobayashi K, Ishikawa Y, Hagiwara K
  • Organizer: The 101st American Association for Cancer ResearchAnnual Meeting 2010
  • Place of Presentation: ワシントンD. C, USA
  • Year and Date: 2010-04-17
• [Presentation] 悪性胸膜中皮腫のSemaphorin 3Bプロモーター領域DNAメチル化解析 (2009)
  • Author(s): 小山信之、張嘉玲、呼群、石川雄一、小林国彦、萩原弘一
  • Organizer: 第50回日本肺癌学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-11-12
• [Presentation] 悪性胸膜中皮腫におけるSemaphorin 3Bプロモーター領域のDNAメチル化解析 (2009)
  • Author(s): 小山信之、張嘉玲、呼群、石川雄一、小林国彦、萩原弘一
  • Organizer: 第68日本癌学会学術総会
  • Place of Presentation: 神奈川
  • Year and Date: 2009-10-30
• [Presentation] Ezh2と肺癌 (2009)
  • Author(s): 小山信之
  • Organizer: 内蒙古医学院セミナー
  • Place of Presentation: 中国
  • Year and Date: 2009-08-27
• [Presentation] Ezh2と肺癌 (2009)
  • Author(s): 小山信之
  • Organizer: 内蒙古医学院セミナー
  • Place of Presentation: 呼和浩得 内蒙古自治区 中国
  • Year and Date: 2009-08-27
• [Presentation] 悪性胸膜中皮腫におけるSEMA3Bメチル化解析 (2009)
  • Author(s): 小山信之、張嘉玲、呼群、石川雄一、小林国彦、萩原弘一
  • Organizer: 第49回日本呼吸器学会学術講演会
  • Year and Date: 2009-05-29
• [Presentation] Enhancer zeste homolog(EZH) 2 expression reduces the survival of the patients with non-small cell lung cancer (2009)
  • Author(s): Koyama N, Huqun
  • Organizer: 100th American Association for Cancer Research
  • Place of Presentation: Denver CO USA
  • Year and Date: 2009-04-22
• [Presentation] Enhancer zeste homolog(EZH)2 expression reduces the survival of the patients with non-small cell lung cancer (2009)
  • Author(s): 小山信之
  • Organizer: 100th American Association for Cancer Research
  • Place of Presentation: Denver CO USA
  • Year and Date: 2009-04-22