4 gene signature will predict the recurrence for stage I lung carcinomas.

• Project/Area Number: 16K09561
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Nippon Medical School
• Principal Investigator: Noro Rintaro 日本医科大学, 医学部, 講師 (50366738)
• Co-Investigator(Kenkyū-buntansha): 清家 正博 日本医科大学, 医学部, 教授 (30366687)
• Research Collaborator: Curtis Harris
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 再発予測 / 肺腺がん / 4遺伝子シグネチャー / 早期肺癌再発予測 / 血管浸潤 / 遺伝子シグネチャー / Ⅰ期非小細胞肺癌 / 術後再発 / 癌 / 臨床呼吸器学

Outline of Final Research Achievements

Surgery with curative intent is the standard treatment for stage I lung adenocarcinoma. However, disease recurrence occurs in a third of patients, and additional adjuvant chemotherapy will be needed for lung carcinomas with high risk for recurrence. There are no validated molecular methods that prospectively identify patients with surgically resected lung carcinoma with early stage at high risk for recurrence. We established the diagnostic system for analyzing 4 gene signature including DLD1, XPO1, BRCA1 and HIF1A, HOXA9 methylation, pathological finding with vascular invasion, ACTN4 activity. We are analyzing how these modality would be able to predict the recurrence with more precision. These system would prove the prognosis for lung carcinomas with early stage.

Academic Significance and Societal Importance of the Research Achievements

肺癌Ⅰ期、特にIA期であっても術後化学療法が必要な予後不良群や不必要な予後良好群が存在し、正確に予測できる再発予測マーカーの同定が必要である。よって新しい再発予測マーカーを構築する。この診断システムにより、術後化学療法を行う必要がある再発高リスク群患者の予後の向上や、不必要な化学療法を行わないことにより、再発低リスク患者のQOLの向上も図ることができる。

Research Products

• [Journal Article] Tenascin XB Is a Novel Diagnostic Marker for Malignant Mesothelioma (2019)
  • Author(s): NAKAYAMA KOJI、SEIKE MASAHIRO、NORO RINTARO、TAKEUCHI SUSUMU、MATSUDA KUNIKO、KUNUGI SHINOBU、KUBOTA KAORU、GEMMA AKIHIKO
  • Journal Title: Anticancer Res. Volume: 39 Pages: 627-633
  • DOI: 10.21873/anticanres.13156
  • Peer Reviewed
• [Journal Article] Interstitial lung disease associated with nanoparticle albumin-bound paclitaxel treatment in patients with lung cancer. (2019)
  • Author(s): Kashiwada T, Saito Y, Terasaki Y, Hisakane K, Takeuchi S, Sugano T, Miyanaga A, Noro R, Minegishi Y, Seike M, Kubota K, Gemma A.
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 1;49(2): Pages: 165-173
  • DOI: 10.1093/jjco/hyy180
  • Peer Reviewed
• [Journal Article] Ankyrin Repeat Domain 1 Overexpression is Associated with Common Resistance to Afatinib and Osimertinib in EGFR-mutant Lung Cancer (2018)
  • Author(s): Takahashi Akiko、Seike Masahiro、Chiba Mika、Takahashi Satoshi、Nakamichi Shinji、Matsumoto Masaru、Takeuchi Susumu、Minegishi Yuji、Noro Rintaro、Kunugi Shinobu、Kubota Kaoru、Gemma Akihiko
  • Journal Title: Sci Rep. Volume: 8 Pages: 14896-14896
  • DOI: 10.1038/s41598-018-33190-8
  • Peer Reviewed / Open Access
• [Journal Article] HOXA9 methylation and blood vessel invasion in FFPE tissues for prognostic stratification of stage I lung adenocarcinoma patients (2018)
  • Author(s): Lissa Delphine、Ishigame Teruhide、Noro Rintaro、Tucker Marguerite J.、Bliskovsky Valery、Shema Steven、Beck Jessica A.、Bowman Elise D.、Harris Curtis C.、Robles Ana I.
  • Journal Title: Lung Cancer. Volume: 122 Pages: 151-159
  • DOI: 10.1016/j.lungcan.2018.05.021
  • Peer Reviewed
• [Journal Article] Prognostic Significance of NSCLC and Response to EGFR-TKIs of EGFR-Mutated NSCLC Based on PD-L1 Expression. (2018)
  • Author(s): Kobayashi K, Seike M, Zou F, Noro R, Chiba M, Ishikawa A, Kunugi S, Kubota K, Gemma A.
  • Journal Title: Anticancer Res. Volume: 38
  • Peer Reviewed
• [Journal Article] AXL and GAS6 co-expression in lung adenocarcinoma as a prognostic classifier. (2017)
  • Author(s): Seike M, Kim CH, Zou F, Noro R, Chiba M, Ishikawa A, Κunugi S, Kubota K, Gemma A
  • Journal Title: Oncol Rep. 2017 Volume: 37 Pages: 3261-3269
  • DOI: 10.3892/or.2017.5594
  • Peer Reviewed
• [Journal Article] Actinin-4 protein overexpression as a predictive biomarker in adjuvant chemotherapy for resected lung adenocarcinoma. (2017)
  • Author(s): Shiraishi H, Fujiwara Y, Kakuya T, Tsuta K, Motoi N, Miura N, Watabe Y, Watanabe SI, Noro R, Nagashima K, Huang W, Yamada T, Asamura H, Ohe Y, Honda K.
  • Journal Title: Biomarkers in Medicine Volume: 11 Pages: 721-731
  • DOI: 10.2217/bmm-2017-0150
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic significance of ABCB1 in stage I lung adenocarcinoma. (2017)
  • Author(s): Zou F, Seike M, Noro R, Kunugi S, Kubota K, Gemma A.
  • Journal Title: Oncol Lett. Volume: 14 Pages: 313-321
  • DOI: 10.3892/ol.2017.6145
  • Peer Reviewed
• [Journal Article] A Drug Interaction between Crizotinib and Warfarin in Non-Small-Cell Lung Cancer: A Case Report (2017)
  • Author(s): Kubomura Y, Ise Y, Wako T, Katayama S, Noro R, Kubota K.
  • Journal Title: J Nippon Med Sch Volume: 84 Issue: 6 Pages: 291-293
  • DOI: 10.1272/jnms.84.291
  • NAID: 130006286539
  • ISSN: 1345-4676, 1347-3409
  • Peer Reviewed
• [Journal Article] A Two-Gene Prognostic Classifier for Early-Stage Lung Squamous Cell Carcinoma in Multiple Large-Scale and Geographically Diverse Cohorts. (2017)
  • Author(s): Noro R, Ishigame T, Walsh N, Shiraishi K, Robles AI, Ryan BM, Schetter AJ, Bowman ED, Welsh JA, Seike M, Gemma A, Skaug V, Mollerup S, Haugen A, Yokota J, Kohno T, Harris CC.
  • Journal Title: J Thorac Oncol Volume: 12(1) Pages: 65-76
  • DOI: 10.1016/j.jtho.2016.08.141
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Interstitial lung disease associated with amrubicin chemotherapy in patients with lung cancer: a single institutional study. (2016)
  • Author(s): Miura Y1, Saito Y2, Atsumi K1, Takeuchi S1, Miyanaga A1, Mizutani H, Minegishi Y, Noro R, Seike M, Kunugi S, Kubota K, Gemma A.
  • Journal Title: Jpn J Clin Oncol Volume: 46(7) Pages: 674-680
  • DOI: 10.1093/jjco/hyw043
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Urinary Metabolite Risk Biomarkers of Lung Cancer: A Prospective Cohort Study. (2016)
  • Author(s): Haznadar M, Cai Q, Krausz KW, Bowman ED, Margono E, Noro R, Thompson MD, Mathé EA, Munro HM, Steinwandel MD, Gonzalez FJ, Blot WJ, Harris CC.
  • Journal Title: Cancer Epidemiol Biomarkers Prev Volume: 25(6) Pages: 978-986
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] miR-200/ZEB axis regulates sensitivity to nintedanib in non-small cell lung cancer cells. (2016)
  • Author(s): Nishijima N, Seike M, Soeno C, Chiba M, Miyanaga A, Noro R, Sugano T, Matsumoto M, Kubota K, Gemma A.
  • Journal Title: Int J Oncol Volume: 48(3) Pages: 937-44
  • DOI: 10.3892/ijo.2016.3331
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Genomic profiling of lung cancer associated with idiopathic pulmonary fibrosis (2018)
  • Author(s): Noro R, Miyanaga A, Fukuizumi A, Seike M, Kubota K, Gemma A
  • Organizer: AACR
  • Int'l Joint Research
• [Presentation] 1.Ⅰ期肺腺癌再発予測システムの構築―術後化学療法とACTN4遺伝子増幅 (2017)
  • Author(s): 野呂林太郎 三浦奈美 本田一文 白石英晶 藤原豊 大江裕一郎 石井源一郎 蔦幸治 淺村尚生 山田哲司 清家正博 久保田馨 弦間昭彦
  • Organizer: 第55回日本癌治療学会
• [Presentation] 2.非小細胞肺がんの転移活性を評価し、術後補助化学療法の効果を予測するバイオマーカーの実用化に関する研究 (2017)
  • Author(s): 野呂林太郎 久保田馨 本田一文
  • Organizer: ジャパン・キャンサーリサーチ・プロジェクト 平成29年度企業向け成果発表会
• [Presentation] ...Abstract 3209: Polo-like kinase 1 as a new molecular target for small cell lung carcinoma (2017)
  • Author(s): Noro R, Seike M, Zou F, Gemma A
  • Organizer: AACR; Cancer Res 2017
  • Int'l Joint Research