Prediction of prognoses from biomarker expression in patients with advanced primary lung cancer by endobronchial ultrasound transbronchial needle aspiration.

• Project/Area Number: 26462140
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Toho University
• Principal Investigator: HATA Yoshinobu 東邦大学, 医学部, 准教授 (90349910)
• Co-Investigator(Kenkyū-buntansha): 伊豫田 明 東邦大学, 医学部, 教授 (10302548) ; 磯部 和順 東邦大学, 医学部, 講師 (70385607) ; 坂本 晋 東邦大学, 医学部, 准教授 (20425440) ; 大塚 創 東邦大学, 医学部, 助教 (70408855) ; 牧野 崇 東邦大学, 医学部, 助教 (30459797)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肺癌 / 術前導入療法 / TUBB3 / ERCC1 / 癌 / 細胞・組織 / 気管支鏡 / 個別化医療

Outline of Final Research Achievements

We analyzed biomarker expression in 20 patients with cN2 stage IIIA lung cancer who underwent induction chemoradiotherapy (carboplatin and docetaxel) and surgery. Immunohistochemistry for class III beta-tubulin (TUBB3) and excision repair cross-complementing 1 (ERCC1) expression was performed in tissue samples obtained before the induction chemoradiotherapy and in surgically resected specimens. Patients who showed a major pathological response exhibited significantly better survival than patients with a minor response. The expression of TUBB3 or ERCC1 in biopsy specimens before induction therapy did not significantly correlate with a pathological response. Patients with high expression of both TUBB3 and ERCC1 showed poor survival, but this was not statistically significant. We postulate that TUBB3 and ERCC1 may act as predictive biomarkers for cN2 stage IIIA lung cancer, albeit with a minor impact. Further studies are required with increased patient numbers.

Research Products

• [Journal Article] Diffuse FDG uptake in bone marrow in patient with granulocyte colony-stimulating factor-producing pleomorphic carcinoma of the lung: a case report. (2017)
  • Author(s): Makino T, hata Y, Otsuka H, Koezuka S, Kikuchi N, Isobe K, Tochigi N, Shibuya K, Homma S, Iyoda A
  • Journal Title: Molecular and Clinical Oncology Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] Primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue with multiple pure ground-glass opacities: a case report (2017)
  • Author(s): Ding X, Makino T, Koezuka S, Azumi T, Otsuka H, Hata Y, Shinya Y, Tochigi N, Shibuya K, Iyoda A
  • Journal Title: Journal of Cardiothoracic Surgery Volume: 12 Issue: 1 Pages: 2-2
  • DOI: 10.1186/s13019-017-0565-9
  • Peer Reviewed / Open Access
• [Journal Article] Association of BIM Deletion Polymorphism and BIM-γ RNA Expression in NSCLC with EGFR Mutation. (2016)
  • Author(s): Isobe K, Kakimoto A, Mikami T, Kaburaki K, Kobayashi H, Yoshizawa T, Makino T, Otsuka H, Sano GO, Sugino K, Sakamoto S, Takai Y, Tochigi N, Iyoda A, Homma S
  • Journal Title: Cancer Genomics Proteomics Volume: 13 Pages: 475-482
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comprehensive biomarkers for personalized treatment in pulmonary large-cell neuroendocrine carcinoma: a comparative analysis with adenocarcinoma. (2016)
  • Author(s): Makino T, Mikami T, hata Y, Otsuka H, Koezuka S, Isobe K, Tochigi N, Shibuya K, Homma S, Iyoda A
  • Journal Title: Annals of Thoracic Surgery Volume: 102 Issue: 5 Pages: 1694-1701
  • DOI: 10.1016/j.athoracsur.2016.04.100
  • Peer Reviewed / Open Access
• [Journal Article] Primary malignant pericardial mesothelioma with increased serum mesothelin diagnosed by surgical pericardial resection: A case report. (2016)
  • Author(s): Kurosawa T, Sugino K, Isobe K, Hata Y, Fukasawa Y, Homma S
  • Journal Title: Molecular and Clinical Oncology Volume: 5 Issue: 5 Pages: 553-556
  • DOI: 10.3892/mco.2016.1019
  • Peer Reviewed / Open Access
• [Journal Article] Clinical features and outcomes of patients with lung cancer and combined pulmonary fibrosis and emphysema (2016)
  • Author(s): Otsuka H, Sugino K, hata Y, Makino T, Koezuka S, Isobe K, Tochigi N, Shibuya K, Homma S, Iyoda A
  • Journal Title: Molecular and Clinical Oncology Volume: 5 Issue: 3 Pages: 273-278
  • DOI: 10.3892/mco.2016.954
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] One-stage operation for thoracic aortic arch aneurysm and left lung carcinoma: a case report (2016)
  • Author(s): Makino T, Kawada K, Masuhara H, hata Y, Otsuka H, Koezuka S, Tochigi N, Shibuya K, Watanabe Y, Iyoda A
  • Journal Title: Journal of Cardiothoracic Surgery Volume: 11 Issue: 1 Pages: 51-51
  • DOI: 10.1186/s13019-016-0440-0
  • Peer Reviewed / Open Access
• [Journal Article] Metachronous second primary lung cancer surgically treated five years or more after the initial surgery (2015)
  • Author(s): Koezuka S, Hata Y, Otsuka H, Makino T, Tochigi N, Shibuya K, Iyoda A
  • Journal Title: Molecular and clinical oncology Volume: 3 Issue: 5 Pages: 1025-1028
  • DOI: 10.3892/mco.2015.594
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Predicted extracapsular invasion of hilar lymph node metastasis by fusion positron emission tomography/computed tomography in patients with lung cancer (2015)
  • Author(s): Makino T, Hata Y, Otsuka H, Koezuka S, Isobe K, Tochigi N, Shiraga N, Shibuya K, Homma S, Iyoda A
  • Journal Title: Molecular and clinical oncology Volume: 3 Issue: 5 Pages: 1035-1040
  • DOI: 10.3892/mco.2015.596
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Usefulness of Nanofluidic Digital PCR Arrays to Quantify T790M Mutation in EGFR-mutant Lung Adenocarcinoma (2015)
  • Author(s): Isobe K, Hata Y, Tochigi N, Kaburaki K, Kobayashi H, Makino T, Otsuka H, Ishida F, Kikuchi N, Hirota N, Sato K, Sano G, Sugino K, Sakamoto S, Takai Y, Shibuya K, Iyoda A, Homma
  • Journal Title: Cancer Genomics & Proteomics Volume: 12 Pages: 31-37
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Placement of self-expandable metallic stents for tracheal stenosis secondary to thyroid cancer (2014)
  • Author(s): Yuasa R, Hata Y, Otsuka H, Makino T, Koezuka S, Sato F, Tamaki K, Sasamoto S, Takagi K, Iyoda A
  • Journal Title: Molecular and Clinical Oncology Volume: 2 Issue: 6 Pages: 1003-1008
  • DOI: 10.3892/mco.2014.350
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 肺大細胞神経内分泌癌切除例におけるSSTRの発現の検討－免疫組織化学染色を用いた肺腺癌との比較検討－ (2016)
  • Author(s): 牧野崇、三上哲夫、栃木直文、秦美暢、肥塚智、安積隆、大塚創、杉野圭史、磯部和順、本間栄、澁谷和俊、伊豫田明
  • Organizer: 第57回日本肺癌学会学術集会（国内学会）
  • Place of Presentation: 福岡国際センター（福岡県福岡市）
  • Year and Date: 2016-12-19
• [Presentation] 進行肺癌における外科治療はどうあるべきか 進行非小細胞肺癌に対する治療戦略 術前導入化学放射線療法後の外科治療について (2016)
  • Author(s): 牧野崇，大塚創，磯部和順，秦美暢，肥塚智，安積隆，杉野圭史，本間栄，栃木直文，渋谷和俊，伊豫田明
  • Organizer: 第78回日本臨床外科学会総会（国内学会）
  • Place of Presentation: グランドプリンスホテル新高輪 国際パミール館（東京都港区）
  • Year and Date: 2016-11-24
• [Presentation] 間質性肺炎合併肺癌に対する胸腔鏡下手術 当院における間質性肺炎合併肺癌に対する胸腔鏡補助下手術 (2016)
  • Author(s): 大塚創，牧野崇，肥塚智，安積隆，秦美暢，伊豫田明
  • Organizer: 第78回日本臨床外科学会総会（国内学会）
  • Place of Presentation: グランドプリンスホテル新高輪 国際パミール館（東京都港区）
  • Year and Date: 2016-11-24
• [Presentation] 肺全摘術 その意義と問題点 原発性肺癌に対する肺全摘術の手術成績について (2016)
  • Author(s): 肥塚智、大塚創、牧野崇、安積隆、秦美暢、伊豫田明
  • Organizer: 第78回日本臨床外科学会総会（国内学会）
  • Place of Presentation: グランドプリンスホテル新高輪 国際パミール館（東京都港区）
  • Year and Date: 2016-11-24
• [Presentation] 肺大細胞神経内分泌癌切除例におけるTopoisomerase-IIの発現の検討 (2016)
  • Author(s): 牧野崇、三上哲夫、栃木直文、秦美暢、肥塚智、大塚創、磯部和順、本間栄、渋谷和俊、伊豫田明
  • Organizer: 第33回日本呼吸器外科学会総会（国内学会）
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-05-12
• [Presentation] LCNEC切除例におけるEGFR遺伝子変異の検討－遺伝子検査と免疫組織学的検査を用いた肺腺癌との比較検討－ (2015)
  • Author(s): 牧野崇，三上哲夫，栃木直文，秦美暢，肥塚智，大塚創，磯部和順，本間栄，渋谷和俊，伊豫田明
  • Organizer: 第56回日本肺癌学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-11-28
• [Presentation] Air leakのある時期の再手術で微小な責任病変を同定できた1例 (2015)
  • Author(s): 松本洋祐，秦美暢，肥塚智，大塚創，牧野崇，石田文昭，本間栄，伊豫田明
  • Organizer: 第154回日本呼吸器内視鏡学会関東支部会
  • Place of Presentation: 東京医科大学病院（東京都新宿区）
  • Year and Date: 2015-09-19
• [Presentation] 分離換気チューブで挿管管理後にDumonステントを留置した右主気管支狭窄の1例 (2015)
  • Author(s): 矢尾尊英，秦美暢，牧野崇，肥塚智，大塚創，石田文昭，本間栄，栃木直文，赤坂喜清，伊豫田明
  • Organizer: 第153回日本呼吸器内視鏡学会関東支部会
  • Place of Presentation: 浦和コミュニティセンター（埼玉県さいたま市）
  • Year and Date: 2015-06-20
• [Presentation] cN2非小細胞肺癌に対するCBDCA/DOCを用いた導入化学放射線療法の検討 (2015)
  • Author(s): 秦美暢，大塚創，牧野崇，肥塚智，磯部和順，本間栄，栃木直文，渋谷和俊，伊豫田明
  • Organizer: 第32回日本呼吸器外科学会総会
  • Place of Presentation: JRホテルクレメント高松（香川県高松市）
  • Year and Date: 2015-05-14
• [Presentation] cN2IIIA非小細胞肺癌に対するCBDCA/DOCを用いた術前導入化学放射線療法 (2015)
  • Author(s): 秦美暢，大塚創，牧野崇，肥塚智，磯部和順，本間栄，栃木直文，渋谷和俊，伊豫田明
  • Organizer: 第115回日本外科学会定期学術集会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-18
• [Presentation] 区域切除術後の局所再発と再発時治療法に関する検討 (2014)
  • Author(s): 秦美暢, 大塚創, 牧野崇, 肥塚智, 笹本修一, 佐藤史朋, 田巻一義, 磯部和順, 鏑木教平, 本間栄, 栃木直文, 渋谷和俊, 伊豫田明
  • Organizer: 第55回日本肺癌学会学術集会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2014-11-16
• [Presentation] EGFR mutaion陽性肺腺癌におけるdigital PCRを用いた治療前原発巣のT790M定量化の試み (2014)
  • Author(s): 磯部和順, 秦美暢, 鏑木教平, 石田文昭, 菊池直, 廣田直, 佐藤敬太, 佐野剛, 杉野圭史, 坂本晋, 高井雄二郎, 栃木直文, 伊豫田明, 渋谷和俊, 本間栄
  • Organizer: 第52回日本癌治療学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-08-29
• [Presentation] 当院における気腫合併特発性肺線維症合併肺癌切除例の検討 (2014)
  • Author(s): 大塚創, 秦美暢, 肥塚智, 牧野崇, 佐藤史朋, 田巻一義, 笹本修一, 磯部和順, 杉野圭史, 栃木直文, 本間栄, 伊豫田明
  • Organizer: 第31回日本呼吸器外科学会総会
  • Place of Presentation: ホテル日航東京（東京都港区）
  • Year and Date: 2014-05-30
• [Presentation] 肺高悪性度神経内分泌癌の術後再発の検討 (2014)
  • Author(s): 牧野崇, 秦美暢, 佐藤史朋, 大塚創, 肥塚智, 田巻一義, 笹本修一, 磯部和順, 栃木直文, 渋谷和俊, 伊豫田明
  • Organizer: 第31回日本呼吸器外科学会総会
  • Place of Presentation: ホテル日航東京（東京都港区）
  • Year and Date: 2014-05-29
• [Presentation] Complication related to EBUS-TBNA in patients with tuberculous lymphadenopathy (2014)
  • Author(s): Hata Y, Sakamoto S, Otsuka H, Sato K, Sato F, Makino T, Sugino K, Isobe K, Shiraga N, Tochigi N, Shibuya K, Homma S, Iyoda A
  • Organizer: 18th World Congress for World Association for Bronchology and Interventional Pulmonology
  • Place of Presentation: Kyoto International conference center (Kyoto city)
  • Year and Date: 2014-04-14
• [Presentation] 病理病期II/III期の80歳以上超高齢者肺癌に対する外科療法の検討 (2014)
  • Author(s): 秦美暢, 大塚創, 牧野崇, 肥塚智, 佐藤史朋, 田巻一義, 笹本修一, 磯部和順, 大国生幸, 栃木直文, 伊豫田明
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2014-04-03
• [Remarks] 東邦大学医療センター大森病院 呼吸器外科ホームページ
  • URL: http://www.lab.toho-u.ac.jp/med/omori/resp_surgery/
• [Remarks] 東邦大学医療センター大森病院 呼吸器外科
  • URL: http://www.lab.toho-u.ac.jp/med/omori/resp_surgery/