Identification of novel disease-specific diagnostic markers and therapeutic targets for interstitial pneumonias

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591148
• 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: Hiroshima University
• Principal Investigator: ISHIKAWA Nobuhisa 広島大学, 医歯薬保健学研究院, 講師 (90423368)
• Project Period (FY): 2011 – 2013
• Keywords: 間質性肺炎 / マイクロアレイ / バイオマーカー / 分子標的治療薬

Research Abstract

Idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP) are subtypes of idiopathic interstitial pneumonia (IIP), which is characterized by alveolar epithelial damage, activation of fibroblast proliferation, and loss of normal pulmonary architecture and function. Clinical differentiation between IPF and NSIP is difficult, and the molecular basis for IIP remains unclear. The study included 12 patients with IIP (IPF, n = 7; NSIP, n = 5). RNA extracted from lung specimens was profiled using Illumina Human WG-6 v3 BeadChips, and an Ingenuity Pathway Analysis was performed to identify altered functional and canonical signaling pathways. Genes and pathways related to cancer, cell death and survival, and cellular growth and proliferation were differentially expressed in IIP patients. These data provide valuable information on the possible mechanisms underlying pulmonary fibrosis, and reveal several potential biomarkers for IIP diagnosis and therapeutic targeting.

Research Products

• [Journal Article] Differences in serum SP-D levels between German and Japanese subjects are associated with SFTPD gene polymorphisms (2014)
  • Author(s): Horimasu Y, Hattori N, Ishikawa N, Tanaka S, Bonella F, Ohshimo S, Guzman J, Costabel U, Kohno N
  • Journal Title: BMC Med Genet Volume: 15(1) Pages: 4
  • Peer Reviewed
• [Journal Article] 第41回箱根呼吸器討論会記録呼吸器疾患の新規バイオマーカーの開発と臨床応用 (2014)
  • Author(s): 石川暢久
  • Journal Title: 呼吸 Volume: 33 Pages: 179-188
• [Journal Article] Different MUC1 gene polymorphisms in German and Japanese ethnicities affect serum KL-6 levels (2013)
  • Author(s): Horimasu Y, Hattori N, Ishikawa N, Kawase S, Tanaka S, Yoshioka K, Yokoyama A, Kohno N, Bonella F, Guzman J, Ohshimo S, Costabel U
  • Journal Title: Respir Med Volume: 106 Pages: 1756-64
  • Peer Reviewed
• [Journal Article] 間質性肺炎マーカーの予後も含めた臨床的意義 (2013)
  • Author(s): 石川暢久,河野修興
  • Journal Title: 日本胸部臨床 Volume: 72 Pages: S19-23
• [Journal Article] Utility of KL-6/MUC1 in the clinical management of interstitial lung diseases (2012)
  • Author(s): Ishikawa N, Hattori N, Yokoyama A, Kohno N
  • Journal Title: Respiratory Investigation Volume: 50 Pages: 3-13
  • Peer Reviewed
• [Journal Article] Krebs von den Lungen-6 (KL-6) is a prognostic biomarker in patients with surgically resected non-small cell lung cancer (2012)
  • Author(s): Tanaka S, Hattori N, Ishikawa N, Shoda H, Takano A, Nishino R, Okada M, Arihiro K, Inai K, Hamada H, Yokoyama A, Kohno N
  • Journal Title: Int J Cancer Volume: 130 Pages: 377-87
  • Peer Reviewed
• [Journal Article] Interferon (alpha, Beta and omega) receptor 2 is a prognostic biomarker for lung cancer (2012)
  • Author(s): Tanaka S, Hattori N, Ishikawa N, Horimasu Y, Deguchi N, Takano A, Tomoda Y, Yoshioka K, Fujitaka K, Arihiro K, Okada M, Yokoyama A, Kohno N
  • Journal Title: Pathobiology Volume: 79 Pages: 24-33
  • Peer Reviewed
• [Journal Article] KL-6が異常高値を示す肺癌の頻度 (2012)
  • Author(s): 石川暢久,河野修興
  • Journal Title: 日本医事新報 Volume: 4613 Pages: 50-51
• [Journal Article] 呼吸器疾患にかかわるバイオマーカー (2012)
  • Author(s): 石川暢久,服部登
  • Journal Title: 呼吸 Volume: 31 Pages: 819 -821
• [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: 17 Pages: 6272-86
  • Peer Reviewed
• [Journal Article] Change in serum KL-6 level from baseline is useful for predicting life-threatening EGFR-TKIs induced interstitial lung disease (2011)
  • Author(s): Kawase S, Hattori N, Ishikawa N, Horimasu Y, Fujitaka K, Furonaka O, Isobe T, Miyoshi S, Hamada H, Yamane T, Yokoyama A, Kohno N
  • Journal Title: Respir Res Volume: 12 Pages: 97
  • Peer Reviewed
• [Journal Article] Ageing and long-term smoking affects KL-6 levels in the lung, induced sputum and plasma (2011)
  • Author(s): Ishikawa N, Mazur W, Toljamo T, Vuopala K, Rönty M, Horimasu Y, Kohno N, Kinnula VL
  • Journal Title: BMC Pulm Med Volume: 11 Pages: 22
  • Peer Reviewed
• [Journal Article] Ageing and smoking contribute to plasma surfactant proteins and protease imbalance with correlations to airway obstruction (2011)
  • Author(s): Ilumets H, Mazur W, Toljamo T, Louhelainen N, Toljamo T, Nieminen P, Kobayashi H, Ishikawa N, KinnulaVL
  • Journal Title: BMC Pulm Med Volume: 11 Pages: 19
  • Peer Reviewed
• [Journal Article] KL-6 Concentration in Pulmonary Epithelial Lining Fluid and Is a Useful Prognostic Indicator in Patients with Acute Respiratory Distress Syndrome (2011)
  • Author(s): Kondo T, Hattori N, Ishikawa N, Murai H, Haruta Y, Hirohashi N, Tanigawa K, Kohno N
  • Journal Title: Respiratory Research Volume: 12 Pages: 32
  • Peer Reviewed
• [Journal Article] Surfactant protein A and KL-6 are elevated in the induced sputum of COPD; a sequential sputum analysis (2011)
  • Author(s): Ishikawa N, Hattori N, Tanaka S, Horimasu Y, Haruta Y, Yokoyama A, Kohno N, Kinnula VL
  • Journal Title: Respiration Volume: 82 Pages: 10-8
  • Peer Reviewed
• [Journal Article] Mucins carrying selectin ligands as predictive biomarkers of disseminated intravascular coagulation complication in acute respiratory distress syndrome (2011)
  • Author(s): Nakashima T, Yokoyama A, Inata J, Ishikawa N, Haruta Y, Hattori N, Kohno N
  • Journal Title: Chest Volume: 139(2) Pages: 296-304
  • 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, Matsuda 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] 【線維化による疾患】特発性肺線維症 (2011)
  • Author(s): 石川暢久,河野修興
  • Journal Title: BIO Clinica Volume: 26 Pages: 1078-84
• [Journal Article] 【特発性間質性肺炎最近の進歩と展望】間質性肺炎のマーカーKL-6,SP-A,SP-D (2011)
  • Author(s): 石川暢久,河野修興
  • Journal Title: 最新医学 Volume: 6 Pages: 1140-5
• [Presentation] Comparison of KL-6, SP-A, SP-D, 8-isoprostane, MMP-9,and TIMP-1 as serum biomarkers for patients with combined pulmonary fibrosis and emphysema (2013)
  • Author(s): Ishikawa N, Matsuda T, Nakashima T, Iwamoto H, Ohshimo S, Fujitaka K, Haruta Y, Murai H, Hattori N, Kohno N
  • Organizer: 18th Congress of the Asian Pacific Society of Respirology
  • Place of Presentation: Yokohama
  • Year and Date: 20131111-14
• [Presentation] KL-6, SP-D and MMP-7 as serum biomarkers for early detection of interstitial lung diseases (2013)
  • Author(s): Ishikawa N, Yoshioka K, Horimasu Y, Iwamoto H, Ohshimo S, Hattori N, Kohno N
  • Organizer: European Respiratory Society Annual Congress
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 20130907-11
• [Presentation] Gene expression profiles of chronic hypersensitivity pneumonitis : Molecular signatures of pulmonary fibrosis (2013)
  • Author(s): Ishikawa N, Taniwaki M, Horimasu Y, Iwamoto H, Ohshimo S, Fujitaka K, Haruta Y, Murai H, Hattori N, Kohno N
  • Organizer: American Thoracic Society International Conference
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 20130517-22
• [Presentation] 気腫合併肺線維症におけるプロテアーゼ・アンチプロテアーゼの不均衡ならびに酸化ストレスの意義 (2013)
  • Author(s): 石川暢久,松田智代,出口奈穂子,堀益靖,大下慎一郎,藤高一慶,春田吉則,村井博,服部登,河野修興
  • Organizer: 第53回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 20130419-21
• [Presentation] 間質性肺炎の早期発見における血清バイオマーカーの有用性に関する検討 (2013)
  • Author(s): 石川暢久,出口奈穂子,岩本博志,大下慎一郎,藤高一慶,春田吉則,村井博,服部登,河野修興
  • Organizer: 第53回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 20130419-21
• [Presentation] Gene expression profiles of idiopathic interstitial pneumonias : Identification of disease-specific diagnostic markers and molecular therapeutic targets (2012)
  • Author(s): Ishikawa N, Hattori N, Taniwaki M, Horimasu Y, Matsuda T, Kohno N
  • Organizer: European Respiratory Society Annual Congress
  • Place of Presentation: Vienna, Austria
  • Year and Date: 20120901-05
• [Book] 間質性肺疾患診療マニュアル・改訂第2版 (2014)
  • Author(s): 石川暢久,河野修興
  • Total Pages: 143-145
  • Publisher: 南江堂 (KL-6)
• [Book] 肺癌腫瘍マーカーの判読のポイント.検査診断学への展望 (2013)
  • Author(s): 石川暢久,河野修興
  • Total Pages: 608-611
  • Publisher: 南江堂
• [Book] 薬剤性肺障害.臨床病態学1巻第2版 (2013)
  • Author(s): 石川暢久,河野修興
  • Total Pages: 309-313
  • Publisher: ヌーベルヒロカワ
• [Book] 肺がん.かんの浸潤・転移 (2011)
  • Author(s): 石川暢久,河野修興
  • Total Pages: 20-27
  • Publisher: 南山堂