Subclassification of lung cancers without driver mutations

• Project/Area Number: 15H04714
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: Ishikawa Yuichi 公益財団法人がん研究会, がん研究所 病理部, 部長 (80222975)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000); Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: 肺癌 / ドライバー変異 / driver変異 / 小細胞癌 / PD-L1 / 非コードRNA / ゲノム不安定性 / メチル化

Outline of Final Research Achievements

Lung cancers without driver mutations (EGFR, KRAS, ALK etc.) are thought to relate with exogenous carcinogens such as smoking. In this study, we focused on exposure to cigarette smoke and asbestos and comprehensively investigated mRNA and miRNA expression. By comparing cumulative smoking, asbestos burden with miRNA expression, we successfully identified specific miRNA to asbestos exposure. Although we attempted to perform integrated analysis using mRNA and miRNA expression, clusters drawn from mRNA and miRNA were not identical. Also, we examined PD-L1 expression in adenocarcinoma and small cell carcinoma and found that PD-L1 expression in small cell carcinoma was unexpectedly a marker for good prognosis.

Research Products

• [Journal Article] Hyalinizing clear cell carcinoma of the bronchial glands: presentation of three cases and pathological comparisons with salivary gland counterparts and bronchial mucoepidermoid carcinomas. (2018)
  • Author(s): Takamatsu M, Sato Y, Muto M, Nagano H, Ninomiya H, Sakakibara R, Baba S, Sakata S, Takeuchi K, Okumura S, Ishikawa Y
  • Journal Title: Modern pathology Volume: 印刷中 Issue: 6 Pages: 923-933
  • DOI: 10.1038/s41379-018-0025-7
  • Peer Reviewed
• [Journal Article] Pulmonary Carcinoids and Low-Grade Gastrointestinal Neuroendocrine Tumors Show Common MicroRNA Expression Profiles, Different from Adenocarcinomas and Small Cell Carcinomas (2017)
  • Author(s): Yoshimoto Toyoki、Motoi Noriko、Yamamoto Noriko、Nagano Hiroko、Ushijima Masaru、Matsuura Masaaki、Okumura Sakae、Yamaguchi Toshiharu、Fukayama Masashi、Ishikawa Yuichi
  • Journal Title: Neuroendocrinology Volume: 106 Issue: 1 Pages: 47-57
  • DOI: 10.1159/000461582
  • Peer Reviewed / Open Access
• [Journal Article] Relationship of tumor PD-L1 (CD274) expression with lower mortality in lung high-grade neuroendocrine tumor (2017)
  • Author(s): Inamura Kentaro、Yokouchi Yusuke、Kobayashi Maki、Ninomiya Hironori、Sakakibara Rie、Nishio Makoto、Okumura Sakae、Ishikawa Yuichi
  • Journal Title: Cancer Medicine Volume: 6 Issue: 10 Pages: 2347-2356
  • DOI: 10.1002/cam4.1172
  • Peer Reviewed / Open Access
• [Journal Article] Tumor B7-H3 (CD276) expression and smoking history in relation to lung adenocarcinoma prognosis. (2017)
  • Author(s): Inamura K, Yokouchi Y, Kobayashi M, Sakakibara R, Ninomiya H, Subat S, Nagano H, Nomura K, Okumura S, Shibutani T, Ishikawa Y.
  • Journal Title: Lung Cancer Volume: 103 Pages: 44-51
  • DOI: 10.1016/j.lungcan.2016.11.013
  • Peer Reviewed
• [Journal Article] Association of tumor TROP2 expression with prognosis varies among lung cancer subtypes (2017)
  • Author(s): Inamura K, Yokouchi Y, Kobayashi M, Ninomiya H, Sakakibara R, Subat S, Nagano H, Nomura K, Okumura S, Shibutani T, Ishikawa Y
  • Journal Title: Oncotarget Volume: 8 Issue: 17 Pages: 28725-28735
  • DOI: 10.18632/oncotarget.15647
  • Peer Reviewed
• [Journal Article] High expression of programmed cell death 1 ligand 1 in lung adenocarcinoma is a poor prognostic factor particularly in smokers and wild-type epidermal growth-factor receptor cases (2017)
  • Author(s): Mori S, Motoi N, Ninomiya H, Matuura Y, Nakao M, Mun M-y, Ikumura S, Nishio M, Morikawa T, Ishikawa Y
  • Journal Title: Pathol Int Volume: 67 Issue: 1 Pages: 37-44
  • DOI: 10.1111/pin.12489
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] SOX2 and Rb1 in esophageal small-cell carcinoma: their possible involvement in pathogenesis (2017)
  • Author(s): Ishida H, Kasajima A, Kamei T, Miura T, Oka N, Yazdani S, Ozawa Y, Fujishima F, Sakurada A, Nakamura Y, Tanaka Y, Kurosumi M, Ishikawa Y, Okada Y, Ohuchi N, Sasano H
  • Journal Title: Mod Pathol Volume: 30 Issue: 5 Pages: 660-671
  • DOI: 10.1038/modpathol.2016.222
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] EBUS-TBNA as a promising method for the evaluation of tumor PD-L1 expression in lung cancer. (2016)
  • Author(s): Sakakibara R, Inamura K, Tambo Y, et al.
  • Journal Title: Clinical Lung Cancer. Volume: 印刷中 Issue: 5 Pages: 527-534
  • DOI: 10.1016/j.cllc.2016.12.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Relationship of tumor PD-L1 expression with EGFR wild type status and poor prognosis in lung adenocarcinoma (2016)
  • Author(s): Inamura K, Yokouchi Y, Sakakibara R, Kobayashi M, Subat S, Ninomiya H, Nagano H, Nomura K, Okumura S, Ishikawa Y.
  • Journal Title: Jpn J Clin Oncol Volume: 46 Issue: 10 Pages: 935-941
  • DOI: 10.1093/jjco/hyw087
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Prognostic significance of CpG island methylator phenotype in surgically resected small cell lung carcinoma. (2016)
  • Author(s): Saito Y, Nagae G, Motoi N, Miyauchi E, Ninomiya H, Uehara H, Mun M, Okumura S, Ohyanagi F, Nishio M, Satoh Y, Aburatani H, Ishikawa Y.
  • Journal Title: Cancer Sci. Volume: 107(3) Issue: 3 Pages: 320-5
  • DOI: 10.1111/cas.12876
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Distinct Characteristics of Small Cell Lung Cancer Correlate With Central or Peripheral Origin Subtyping Based on Location and Expression of Transcription Factor TTF-1. (2015)
  • Author(s): Miyauchi E, Motoi N, Ono H, et al.
  • Journal Title: Medicine Volume: 94 Issue: 51 Pages: e2324-e2324
  • DOI: 10.1097/md.0000000000002324
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pulmonary Adenocarcinoma In Situ: Analyses of a Large Series With Reference to Smoking, Driver Mutations, and Receptor Tyrosine Kinase Pathway Activation. (2015)
  • Author(s): Sato S, Motoi N, Hiramatsu M, et al.
  • Journal Title: Am J Surg Pathol Volume: 39 Issue: 7 Pages: 912-921
  • DOI: 10.1097/pas.0000000000000458
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 肺癌病理分類の新しい動向 (2015)
  • Author(s): 石川雄一
  • Journal Title: 肺癌 Volume: 55 Pages: 810-812
  • NAID: 130005112750
• [Journal Article] 個別化医療時代における肺がんの病理分類 (2015)
  • Author(s): 二宮浩範、石川雄一
  • Journal Title: 最新医学 Volume: 70 Pages: 2449-2454
• [Presentation] PD-L1 expression in lung cancer (2016)
  • Author(s): Ishikawa Y
  • Organizer: The 11-th Annual Meeting of the Asia Pacific Society for Molecular Immunohistology
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2016-12-11
  • Int'l Joint Research / Invited
• [Presentation] Common origin of carcinoids of the lung and gastrointestinal tract identified by miRNA profiling (2016)
  • Author(s): Ishikawa Y, Yoshimoto T, Motoi N, Yamamoto N, Fukuyama M
  • Organizer: XXXI International Congress of the International Academy of Pathology. Germany
  • Place of Presentation: Koeln, Germany
  • Year and Date: 2016-09-25
  • Int'l Joint Research
• [Presentation] Neuroendocrine tumors of the lung and other organs particularly digestive organs: their histogenesis and pathology diagnosis (2015)
  • Author(s): Ishikawa Y
  • Organizer: 6-th CME Course of Thoracic Tumor and 2-nd Meeting of Committee of Thoracic Disease. Chinese Society of Pathology
  • Place of Presentation: Xiamen, Fujian Province
  • Year and Date: 2015-06-26
  • Int'l Joint Research / Invited
• [Presentation] Neuroendocrine carcinoma of the lung (2015)
  • Author(s): Ishikawa Y
  • Organizer: Pathology Expert Forum: The WHO Classification of Lung Tumors 2015. Taiwan Society of Pathology and Taiwan Division of IAP
  • Place of Presentation: Taipei
  • Year and Date: 2015-05-17
  • Int'l Joint Research / Invited