Elucidation of molecular expression in patients with idiopathic interstitial pneumonia using multidisciplinary proteomic analysis and its clinical application

2020 Fiscal Year Annual Research Report

• Project/Area Number: 18K15947
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: 穗積 宏尚 浜松医科大学, 医学部附属病院, 助教 (40771457)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 特発性肺線維症 / プロテオミクス / バイオマーカー

Outline of Annual Research Achievements

特発性間質性肺炎は、7つ以上の独立した疾患に分類され、それぞれ治療戦略や予後が異なる。それゆえに、各疾患を正確に診断することが重要であるが、それは決して容易ではない。さらに、患者の臨床経過や治療反応性には個人差があり、その予測は難しい。したがって、診断に貢献できる疾患特異的バイオマーカーや、疾患活動性を評価できるマーカー、治療反応性や予後を予測できるマーカーがあれば、個々の患者に最良な治療戦略を選択し、予後・QOLの改善や、有害事象の減少に貢献できる。
[1]特発性肺線維症（IPF）における疾患進行および予後を予測する血清バイオマーカーの開発
前年度までにLS-MS/MSを用いたショットガンプロテオミクス法にて発見したバイオマーカー候補26種類のうち、3つのマーカー（S100A4、CIRBP、14-3-3γ）がIPF患者の1年後の呼吸機能の悪化（疾患進行）や生命予後不良と関連し、外科的肺生検組織における線維化領域で高発現していることがわかった。この3つのマーカーのうち、CIRBP高値はIPF患者の疾患進行や生命予後不良と関連し、その結果は2施設の後ろ向き研究で検証された。今後の実用化を進める方針である。
[2]IPFにおける早期診断に有用な病理組織または血清バイオマーカーの開発
IPF患者から外科的肺生検によって採取された肺組織を用いて、ショットガンプロテオミクス法にてIPF患者特異的に組織発現するタンパク分子を探索した。その結果、数種類の特異的タンパク候補を同定した。これらの局在を免疫染色にて確認したが、再現性のある結果が得られず、今回の解析ではIPFに特異的なマーカーとなりうるかどうか決定できなかった。

Research Products

• [Journal Article] Clinical Significance of Interstitial Lung Disease and Its Acute Exacerbation in Microscopic Polyangiitis (2021)
  • Author(s): Hozumi H, Kono M, Hasegawa H, Yasui H, Suzuki Y, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Inui N, Nakamura Y, Yokomura K, Nakamura H, Suda T.
  • Journal Title: Chest Volume: S0012-3692(21) Pages: -
  • DOI: 10.1016/j.chest.2021.01.083.
  • Peer Reviewed
• [Journal Article] Risk Factors for Pneumonia and Death in Adult Patients With Seasonal Influenza and Establishment of Prediction Scores: A Population-Based Study (2021)
  • Author(s): Miyashita K, Nakatani E, Hozumi H, Sato Y, Miyachi Y, Suda T.
  • Journal Title: Open Forum Infectious Diseases Volume: 8 Pages: -
  • DOI: 10.1093/ofid/ofab068.
  • Peer Reviewed / Open Access
• [Journal Article] Conventional type 2 lung dendritic cells are potent inducers of follicular helper T cells in the asthmatic lung (2021)
  • Author(s): Sakurai S, Furuhashi K, Horiguchi R, Nihashi F, Yasui H, Karayama M, Suzuki Y, Hozumi H, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Suda T.
  • Journal Title: Allergology International Volume: S1323-8930(21) Pages: -
  • DOI: 10.1016/j.alit.2021.01.008.
  • Peer Reviewed / Open Access
• [Journal Article] Cluster analysis-based clinical phenotypes of idiopathic interstitial pneumonias: associations with acute exacerbation and overall survival (2021)
  • Author(s): Aoshima Y, Karayama M, Horiike Y, Mori K, Yasui H, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Inui N, Suda T.
  • Journal Title: BMC Pulmonary Medicine Volume: 21 Pages: -
  • DOI: 10.1186/s12890-021-01428-3.
  • Peer Reviewed / Open Access
• [Journal Article] Predictors for bronchoalveolar lavage recovery failure in diffuse parenchymal lung disease (2021)
  • Author(s): Koda K, Hozumi H, Yasui H, Suzuki Y, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Inui N, Nakamura Y, Suda T.
  • Journal Title: Scientific Reports Volume: 11 Pages: -
  • DOI: 10.1038/s41598-021-81313-5.
  • Peer Reviewed / Open Access
• [Journal Article] Pneumothorax in Patients with Idiopathic Pleuroparenchymal Fibroelastosis: Incidence, Clinical Features, and Risk Factors (2021)
  • Author(s): Kono M, Nakamura Y, Enomoto Y, Yasui H, Hozumi H, Karayama M, Suzuki Y, Furuhashi K, Miki Y, Hashimoto D, Fujisawa T, Enomoto N, Inui N, Kaida Y, Yokomura K, Koshimizu N, Toyoshima M, Imokawa S, Yamada T, Shirai T, Hayakawa H, Nakamura H, Suda T.
  • Journal Title: Respiration Volume: 100 Pages: 19-26
  • DOI: 10.1159/000511965.
  • Peer Reviewed
• [Journal Article] Quality of dying and death in patients with interstitial lung disease compared with lung cancer: an observational study (2021)
  • Author(s): Koyauchi T, Suzuki Y, Sato K, Hozumi H, Karayama M, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Inui N, Yokomura K, Imokawa S, Nakamura H, Morita T, Suda T.
  • Journal Title: Thorax Volume: 76 Pages: 248-255
  • DOI: 10.1136/thoraxjnl-2020-215917.
  • Peer Reviewed
• [Journal Article] Comprehensive assessment of multiple tryptophan metabolites as potential biomarkers for immune checkpoint inhibitors in patients with non-small cell lung cancer (2021)
  • Author(s): Karayama M, Masuda J, Mori K, Yasui H, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Inui N, Suda T, Maekawa M, Sugimura H, Takada A.
  • Journal Title: Clinical and Translational Oncology Volume: 23 Pages: 418-423
  • DOI: 10.1007/s12094-020-02421-8.
  • Peer Reviewed / Open Access
• [Journal Article] Cause of mortality and sarcopenia in patients with idiopathic pulmonary fibrosis receiving antifibrotic therapy (2021)
  • Author(s): Suzuki Y, Aono Y, Kono M, Hasegawa H, Yokomura K, Naoi H, Hozumi H, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Nakamura H, Suda T.
  • Journal Title: Respirology Volume: 26 Pages: 171-179
  • DOI: 10.1111/resp.13943.
  • Peer Reviewed
• [Journal Article] Prednisolone and tacrolimus versus prednisolone and cyclosporin A to treat polymyositis/dermatomyositis-associated ILD: A randomized, open-label trial (2021)
  • Author(s): Fujisawa T, Hozumi H, Kamiya Y, Kaida Y, Akamatsu T, Kusagaya H, Satake Y, Mori K, Mikamo M, Matsuda H, Yokomura K, Koshimizu N, Toyoshima M, Imokawa S, Yasui H, Suzuki Y, Karayama M, Furuhashi K, Enomoto N, Nakamura Y, Inui N, Suda T.
  • Journal Title: Respirology Volume: 26 Pages: 370-377
  • DOI: 10.1111/resp.13978.
  • Peer Reviewed
• [Journal Article] Assessment of Immune-Related Interstitial Lung Disease in Patients With NSCLC Treated with Immune Checkpoint Inhibitors: A Multicenter Prospective Study (2020)
  • Author(s): Suzuki Y, Karayama M, Uto T, Fujii M, Matsui T, Asada K, Kusagaya H, Kato M, Matsuda H, Matsuura S, Toyoshima M, Mori K, Ito Y, Koyauchi T, Yasui H, Hozumi H, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Suda T.
  • Journal Title: Journal of Thoracic Oncology Volume: 15 Pages: 1317-1327
  • DOI: 10.1016/j.jtho.2020.04.002.
  • Peer Reviewed
• [Journal Article] Palliative Care for Idiopathic Pulmonary Fibrosis Patients: Pulmonary Physicians' View (2020)
  • Author(s): Akiyama N, Fujisawa T, Morita T, Mori K, Yasui H, Hozumi H, Suzuki Y, Karayama M, Furuhashi K, Enomoto N, Nakamura Y, Inui N, Suda T.
  • Journal Title: The Journal of Pain and Symptom Management Volume: 60 Pages: 933-940
  • DOI: 10.1016/j.jpainsymman.2020.06.012.
  • Peer Reviewed
• [Journal Article] Acute exacerbation of unclassifiable idiopathic interstitial pneumonia: comparison with idiopathic pulmonary fibrosis (2020)
  • Author(s): Enomoto N, Naoi H, Aono Y, Katsumata M, Horiike Y, Yasui H, Karayama M, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Inui N, Nakamura Y, Suda T.
  • Journal Title: Therapeutic Advances in Respiratory Disease Volume: 14 Pages: -
  • DOI: 10.1177/1753466620935774.
  • Peer Reviewed / Open Access
• [Journal Article] Pneumothorax in connective tissue disease-associated interstitial lung disease (2020)
  • Author(s): Nishimoto K, Fujisawa T, Yoshimura K, Enomoto Y, Yasui H, Hozumi H, Karayama M, Suzuki Y, Furuhashi K, Enomoto N, Nakamura Y, Inui N, Sumikawa H, Johkoh T, Suda T.
  • Journal Title: PLoS One Volume: 15 Pages: e0235624
  • DOI: 10.1371/journal.pone.0235624.
  • Peer Reviewed / Open Access
• [Journal Article] Development of a novel T cell-oriented vaccine using CTL/Th-hybrid epitope long peptide and biodegradable microparticles, against an intracellular bacterium (2020)
  • Author(s): Tanaka K, Enomoto N, Uehara M, Furuhashi K, Sakurai S, Yasui H, Karayama M, Hozumi H, Suzuki Y, Fujisawa T, Inui N, Nakamura Y, Nagata T, Suda T.
  • Journal Title: Microbiology and Immunology Volume: 64 Pages: 666-678
  • DOI: 10.1111/1348-0421.12836.
  • Peer Reviewed
• [Journal Article] Erlotinib and bevacizumab in elderly patients ?75?years old with non-small cell lung cancer harboring epidermal growth factor receptor mutations (2020)
  • Author(s): Aoshima Yoichiro、Karayama Masato、Inui Naoki、Yasui Hideki、Hozumi Hironao、Suzuki Yuzo、Furuhashi Kazuki、Fujisawa Tomoyuki、Enomoto Noriyuki、Nakamura Yutaro、Mikamo Masashi、Matsuura Shun、Kusagaya Hideki、Kaida Yusuke、Uto Tomohiro、Hashimoto Dai、Matsui Takashi、Asada Kazuhiro、Suda Takafumi
  • Journal Title: Investigational New Drugs Volume: 39 Pages: 210～216
  • DOI: 10.1007/s10637-020-00988-1
  • Peer Reviewed
• [Journal Article] Disease course and prognosis of pleuroparenchymal fibroelastosis compared with idiopathic pulmonary fibrosis (2020)
  • Author(s): Suzuki Y, Fujisawa T, Sumikawa H, Tanaka T, Sugimoto C, Kono M, Hozumi H, Karayama M, Furuhashi K, Enomoto N, Nakamura Y, Inui N, Suda T.
  • Journal Title: Respiratory Medicine Volume: 171 Pages: 106078
  • DOI: 10.1016/j.rmed.2020.106078.
  • Peer Reviewed
• [Journal Article] Prognostic significance of forced vital capacity decline prior to and following antifibrotic therapy in idiopathic pulmonary fibrosis (2020)
  • Author(s): Aono Y, Nakamura Y, Kono M, Nakamura H, Yokomura K, Imokawa S, Toyoshima M, Yasui H, Hozumi H, Karayama M, Suzuki Y, Furuhashi K, Enomoto N, Fujisawa T, Inui N, Suda T.
  • Journal Title: Therapeutic Advances in Respiratory Disease Volume: 14 Pages: -
  • DOI: 10.1177/1753466620953783.
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of Programmed Death Ligand 1 (PD-L1) Gene Amplification and Response to Nivolumab Monotherapy in Non-small Cell Lung Cancer (2020)
  • Author(s): Inoue Y, Yoshimura K, Nishimoto K, Inui N, Karayama M, Yasui H, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Asada K, Uto T, Fujii M, Matsui T, Matsuura S, Hashimoto D, Toyoshima M, Kusagaya H, Matsuda H, Inami N, Kaida Y, Niwa M, Ito Y, Sugimura H, Suda T.
  • Journal Title: JAMA Network Open Volume: 3 Pages: e2011818
  • DOI: 10.1001/jamanetworkopen.2020.11818.
  • Peer Reviewed / Open Access
• [Journal Article] Influenza A virus enhances ciliary activity and mucociliary clearance via TLR3 in airway epithelium (2020)
  • Author(s): Kamiya Y, Fujisawa T, Katsumata M, Yasui H, Suzuki Y, Karayama M, Hozumi H, Furuhashi K, Enomoto N, Nakamura Y, Inui N, Setou M, Ito M, Suzuki T, Ikegami K, Suda T.
  • Journal Title: Respiratory Research Volume: 21 Pages: 282
  • DOI: 10.1186/s12931-020-01555-1.
  • Peer Reviewed / Open Access
• [Journal Article] Clinical, radiological, and pathological evaluation of "NSIP with OP overlap" pattern compared with NSIP in patients with idiopathic interstitial pneumonias (2020)
  • Author(s): Enomoto N, Sumikawa H, Sugiura H, Kitani M, Tanaka T, Hozumi H, Fujisawa T, Suda T.
  • Journal Title: Respiratory Medicine Volume: 174 Pages: 106201
  • DOI: 10.1016/j.rmed.2020.106201.
  • Peer Reviewed
• [Presentation] 14-3-3γ Protein: A Novel Serum Biomarker for Predicting Prognosis in Idiopathic Pulmonary Fibrosis. (2020)
  • Author(s): Hozumi H, Isayama T, Okada J, Sugiura K, Yasui H, Suzuki Y, Kono M, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Inui N, Nakamura Y, Hayakawa H, Suda T
  • Organizer: American Thoracic Society 2020 International Conference
  • Int'l Joint Research
• [Presentation] 特発性肺線維症における14-3-3γ蛋白の臨床的有用性 (2020)
  • Author(s): 穗積宏尚, 安井秀樹, 鈴木勇三, 河野雅人, 柄山正人, 古橋一樹, 榎本紀之, 藤澤朋幸, 乾直輝, 中村祐太郎, 須田隆文
  • Organizer: 第60回日本呼吸器学会学術講演会