多角的なプロテオーム解析による特発性間質性肺炎の分子発現解明と臨床応用

2019 Fiscal Year Research-status 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

[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、タンパクB、タンパクC）がIPF患者の1年後の呼吸機能の悪化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、S100A4については英語論文化された（Respirology 2019）。また、これらのマーカーに関し、特許出願を行った（出願番号 特願2019-111310）。現在、多施設共同でのValidation研究を行っている。
[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患者特異的に組織発現するタンパク分子を探索中である。現在、数種類の特異的タンパクが同定されており、これらの局在を免疫染色にて確認した。今後は、多数例でValidationを行う予定である。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

特発性肺線維症の新規バイオマーカーのValidation研究が順調に進んでいるため。

Strategy for Future Research Activity

[1]多施設共同のValidation研究を継続し、新規バイオマーカーの有用性を検証する。
[2]病理組織から同定された特異的タンパクの絞り込みを行い、Validationを行う。

Causes of Carryover

理由：研究室の再移転があり、実験の延期が生じたため。
また、同定された候補バイオマーカーの数が少なく、測定検査キットの購入費用が削減できたため。
計画：延期されたレクチンアレイ等の実験を行う予定である。

Research Products

• [Journal Article] Predictors of acute exacerbation in biopsy-proven idiopathic pulmonary fibrosis. (2020)
  • Author(s): Kishaba T, Hozumi H, Fujisawa T, Nei Y, Enomoto N, Sugiura H, Kitani M, Suda T.
  • Journal Title: Respiratory Investigation Volume: - Pages: -
  • DOI: 10.1016/j.resinv.2020.02.004.
  • Peer Reviewed
• [Journal Article] Intravoxel incoherent motion magnetic resonance imaging for predicting the long-term efficacy of immune checkpoint inhibitors in patients with non-small-cell lung cancer. (2020)
  • Author(s): Karayama M, Yoshizawa N, Sugiyama M, Mori K, Yasui H, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Inui N, Goshima S, Suda T, Takehara Y.
  • Journal Title: Lung Cancer Volume: 143 Pages: 47-54
  • DOI: 10.1016/j.lungcan.2020.03.013.
  • Peer Reviewed
• [Journal Article] Pulse oximetric saturation to fraction of inspired oxygen (SpO2/FIO2) ratio 24 hours after high-flow nasal cannula (HFNC) initiation is a good predictor of HFNC therapy in patients with acute exacerbation of interstitial lung disease. (2020)
  • Author(s): Koyauchi T, Yasui H, Enomoto N, Hasegawa H, Hozumi H, Suzuki Y, Karayama M, Furuhashi K, Fujisawa T, Nakamura Y, Inui N, Yokomura K, Suda T.
  • Journal Title: Therapeutic Advances in Respiratory Disease Volume: 14 Pages: -
  • DOI: 10.1177/1753466620906327.
  • Peer Reviewed / Open Access
• [Journal Article] Clinical significance of serum S100 calcium‐binding protein A4 in idiopathic pulmonary fibrosis (2019)
  • Author(s): Akiyama Norimichi、Hozumi Hironao、Isayama Takuya、Okada Jun、Sugiura Katsunori、Yasui Hideki、Suzuki Yuzo、Kono Masato、Karayama Masato、Furuhashi Kazuki、Enomoto Noriyuki、Fujisawa Tomoyuki、Inui Naoki、Nakamura Yutaro、Suda Takafumi
  • Journal Title: Respirology Volume: - Pages: -
  • DOI: 10.1111/resp.13707
  • Peer Reviewed
• [Journal Article] Macrophage Mannose Receptor CD206 Predicts Prognosis in Community-acquired Pneumonia. (2019)
  • Author(s): Tsuchiya K, Suzuki Y, Yoshimura K, Yasui H, Karayama M, Hozumi H, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Yokomura K, Suda T.
  • Journal Title: Scientific Reports Volume: 9 Pages: -
  • DOI: 10.1038/s41598-020-58958-9.
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic factors for primary Sjögren's syndrome-associated interstitial lung diseases. (2019)
  • Author(s): Kamiya Y, Fujisawa T, Kono M, Nakamura H, Yokomura K, Koshimizu N, Toyoshima M, Imokawa S, Sumikawa H, Johkoh T, Yasui H, Hozumi H, Suzuki Y, Karayama M, Furuhashi K, Enomoto N, Nakamura Y, Inui N, Suda T.
  • Journal Title: Respiratory Medicine Volume: 159 Pages: -
  • DOI: 10.1016/j.rmed.2019.105811.
  • Peer Reviewed
• [Journal Article] Effect of PD-1 inhibitor on exhaled nitric oxide and pulmonary function in non-small cell lung cancer patients with and without COPD. (2019)
  • Author(s): Suzuki Y, Inui N, Karayama M, Imokawa S, Yamada T, Yokomura K, Asada K, Kusagaya H, Kaida Y, Matsuda H, Koshimizu N, Toyoshima M, Masuda M, Hayakawa H, Hozumi H, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Suda T.
  • Journal Title: International Journal of Chronic Obstructive Pulmonary Disease Volume: 14 Pages: 1867-1877
  • DOI: 10.2147/COPD.S214610.
  • Peer Reviewed / Open Access
• [Journal Article] Once-daily fluticasone furoate/vilanterol combination versus twice-daily budesonide/formoterol combination in the treatment of controlled stable asthma: a randomized crossover trial. (2019)
  • Author(s): Furuhashi K, Fujisawa T, Hashimoto D, Kamiya Y, Yasui H, Karayama M, Suzuki Y, Hozumi H, Enomoto N, Nakamura Y, Inui N, Suda T.
  • Journal Title: Journal of Asthma and Allergy Volume: 12 Pages: 253-261
  • DOI: 10.2147/JAA.S223093.
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic impact of an early marginal decline in forced vital capacity in idiopathic pulmonary fibrosis patients treated with pirfenidone. (2019)
  • Author(s): Kono M, Nakamura Y, Enomoto N, Saito G, Koyanagi Y, Miyashita K, Tsutsumi A, Kobayashi T, Yasui H, Hozumi H, Karayama M, Suzuki Y, Furuhashi K, Miki Y, Hashimoto D, Fujisawa T, Inui N, Suda T, Nakamura H.
  • Journal Title: Respiratory Investigation Volume: 57 Pages: 552-560
  • DOI: 10.1016/j.resinv.2019.07.003.
  • Peer Reviewed
• [Journal Article] Body composition changes successfully classify prognosis in patients with mycobacterium avium complex lung disease. (2019)
  • Author(s): Akahori D, Suzuki Y, Yokomura K, Shirai M, Yasui H, Hozumi H, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Hayakawa H, Suda T.
  • Journal Title: Journal of Infection Volume: 79 Pages: 341-348
  • DOI: 10.1016/j.jinf.2019.07.014.
  • Peer Reviewed
• [Journal Article] Analysis of serum adiponectin and leptin in patients with acute exacerbation of idiopathic pulmonary fibrosis. (2019)
  • Author(s): Enomoto N, Oyama Y, Yasui H, Karayama M, Hozumi H, Suzuki Y, Kono M, Furuhashi K, Fujisawa T, Inui N, Nakamura Y, Suda T.
  • Journal Title: Scientific Reports Volume: 9 Pages: -
  • DOI: 10.1038/s41598-019-46990-3.
  • Peer Reviewed / Open Access
• [Journal Article] Clinical features of three-dimensional computed tomography-based radiologic phenotypes of chronic obstructive pulmonary disease. (2019)
  • Author(s): Karayama M, Inui N, Yasui H, Kono M, Hozumi H, Suzuki Y, Furuhashi K, Hashimoto D, Enomoto N, Fujisawa T, Nakamura Y, Watanabe H, Suda T.
  • Journal Title: International Journal of Chronic Obstructive Pulmonary Disease Volume: 14 Pages: 1333-1342
  • DOI: 10.2147/COPD.S207267.
  • Peer Reviewed / Open Access
• [Journal Article] Frequency and clinical relevance of anti-cyclic citrullinated peptide antibody in idiopathic interstitial pneumonias. (2019)
  • Author(s): Katsumata M, Hozumi H, Yasui H, Suzuki Y, Kono M, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Inui N, Nakamura Y, Suda T.
  • Journal Title: Respiratory Medicince Volume: 154 Pages: 102-108
  • DOI: 10.1016/j.rmed.2019.06.016.
  • Peer Reviewed
• [Journal Article] Successful classification of macrophage-mannose receptor CD206 in severity of anti-MDA5 antibody positive dermatomyositis associated ILD. (2019)
  • Author(s): Horiike Y, Suzuki Y, Fujisawa T, Yasui H, Karayama M, Hozumi H, Furuhashi K, Enomoto N, Nakamura Y, Inui N, Ogawa N, Suda T.
  • Journal Title: Rheumatology Volume: 58 Pages: 2143-2152
  • DOI: 10.1093/rheumatology/kez185.
  • Peer Reviewed
• [Journal Article] Physiological and morphological differences of airways between COPD and asthma?COPD overlap (2019)
  • Author(s): Karayama Masato、Inui Naoki、Yasui Hideki、Kono Masato、Hozumi Hironao、Suzuki Yuzo、Furuhashi Kazuki、Hashimoto Dai、Enomoto Noriyuki、Fujisawa Tomoyuki、Nakamura Yutaro、Watanabe Hiroshi、Suda Takafumi
  • Journal Title: Scientific Reports Volume: 9 Pages: -
  • DOI: 10.1038/s41598-019-44345-6
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Significance of Serum Chitotriosidase Level in Anti-MDA5 Antibody?positive Dermatomyositis-associated Interstitial Lung Disease (2019)
  • Author(s): Fujisawa Tomoyuki、Hozumi Hironao、Yasui Hideki、Suzuki Yuzo、Karayama Masato、Furuhashi Kazuki、Enomoto Noriyuki、Nakamura Yutaro、Inui Naoki、Suda Takafumi
  • Journal Title: The Journal of Rheumatology Volume: 46 Pages: 935～942
  • DOI: 10.3899/jrheum.180825
  • Peer Reviewed
• [Journal Article] Olanzapine-containing antiemetic therapy for the prevention of carboplatin-induced nausea and vomiting. (2019)
  • Author(s): Tanaka K, Inui N, Karayama M, Yasui H, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Kusagaya H, Matsuura S, Uto T, Hashimoto D, Matsui T, Asada K, Suda T.
  • Journal Title: Cancer Chemotherapy and Pharmacology Volume: 84 Pages: 147-153
  • DOI: 10.1007/s00280-019-03868-5.
  • Peer Reviewed
• [Patent(Industrial Property Rights)] 特発性肺線維症の予後予測方法 (2019)
  • Inventor(s): 穗積宏尚
  • Industrial Property Rights Holder: 浜松医科大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特願2019-111310