Aquisition of novel useful predictive biomarkers of the efficacy of adjuvant chemotherapy in patients with non-small cell lung cancer and validate of those utilities.

• Project/Area Number: 17K08729
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Kitasato University
• Principal Investigator: Sato Yuichi 北里大学, 医療衛生学部, 教授 (30178793)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 非小細胞性肺癌 / 術後補助化学療法 / 治療予測マーカー / Nestin / S100A16 / TRAP1 / galectin-3 / 治療効果予測マーカー / 予後予測マーカー / 肺癌 / 呼吸器・縦隔

Outline of Final Research Achievements

Platinum-based adjuvant chemotherapy after complement resection has become a standard treatment for patients with stage II and IIIA non-small cell lung cancer. However, not all patients exhibited survival benefits. Therefore, the development of predictive biomarkers for selecting a subgroup of patients who may show improved survival after those treatment is important. In this project, I explored novel predictive biomarkers of the effect of platinum-based adjuvant chemotherapy via several kinds of proteomics techniques. Then, I validated their utility for predicting the prognosis of the patients with completely resected non-small cell lung cancer receiving platinum-based adjuvant chemotherapy. I reported that S100A16, nestin, TRAP1 and galectin-3 were promising candidate as prognostic biomarkers for these patients.

Academic Significance and Societal Importance of the Research Achievements

ステージIIからIIIAの非小細胞性肺癌患者の治療には術後補助化学療法としてプラチナ製剤を基本とした多剤併用療法が推奨されているが、奏効性が乏しい患者、副作用が強い患者も存在する。しかし、治療効果を事前に予測する試みはほとんど行われていない。治療前に効果が予測出来れば、免疫チェックポイント阻害剤の使用など他の治療法への変更が可能となる。今回、治療効果予測マーカーの獲得を目指した研究を行った。

Research Products

• [Journal Article] TRAP1 is a predictive biomarker of platinum-based adjuvant chemotherapy benefits in patients with resected lung adenocarcinoma (2020)
  • Author(s): Kuchitsu Y, Nagashio R, Igawa S, Kusuhara S, Tsuchiya B, Ichinoe M, Satoh Y, Naoki K, Murakumo Y, Saegusa M, Sato Y.
  • Journal Title: Biomedical Research Volume: 41 Issue: 1 Pages: 53-65
  • DOI: 10.2220/biomedres.41.53
  • NAID: 130007801495
  • ISSN: 0388-6107, 1880-313X
  • Year and Date: 2020-02-01
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic significance of NAP1L1 expression in patients with early lung adenocarcinoma (2020)
  • Author(s): Nagashio Ryo、 Kuchitsu Yuki、 Igawa Satoshi、 Kusuhara Seiichiro、 Naoki Katsuhiko、 Satoh Yukitoshi、 Ichinoe Masaaki、 Murakumo Yoshiki、 Saegusa Makoto、 Sato Yuichi
  • Journal Title: Biomedical Research Volume: 41
  • NAID: 130007853774
  • Peer Reviewed / Open Access
• [Journal Article] <b>Clinicopathological and prognostic significance of nuclear UGDH localization in lung adenocar</b><b>cinoma</b> (2019)
  • Author(s): HAGIUDA Daisuke、NAGASHIO Ryo、ICHINOE Masaaki、TSUCHIYA Benio、IGAWA Satoshi、NAOKI Katsuhiko、SATOH Yukitoshi、MURAKUMO Yoshiki、SAEGUSA Makoto、SATO Yuichi
  • Journal Title: Biomedical Research Volume: 40 Issue: 1 Pages: 17-27
  • DOI: 10.2220/biomedres.40.17
  • NAID: 130007602849
  • ISSN: 0388-6107, 1880-313X
  • Year and Date: 2019-02-01
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic significance of IMMT expression in surgically-resected lung adenocarcinoma. (2019)
  • Author(s): Hiyoshi Y, Ichinoe M, Nagashio R, Hagiuda D, Kobayashi M, Kusuhara S, Igawa S, Shiomi K, Goshima N, Murakumo Y, Saegusa M, Satoh Y, Masuda N, Naoki K.
  • Journal Title: Thorac Cancer Volume: 10 Issue: 11 Pages: 2142-2151
  • DOI: 10.1111/1759-7714.13200
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic significance of G6PD expression and localization in lung adenocarcinoma (2019)
  • Author(s): Nagashio Ryo、Oikawa Shota、Yanagita Kengo、Hagiuda Daisuke、Kuchitsu Yuki、Igawa Satoshi、Naoki Katsuhiko、Satoh Yukitoshi、Ichinoe Masaaki、Murakumo Yoshiki、Saegusa Makoto、Sato Yuichi
  • Journal Title: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics Volume: 1867 Issue: 1 Pages: 38-46
  • DOI: 10.1016/j.bbapap.2018.05.005
  • Peer Reviewed / Open Access
• [Journal Article] Basigin expression as a prognostic indicator in stage I pulmonary adenocarcinoma (2018)
  • Author(s): Matsumoto Toshihide、Nagashio Ryo、Ryuge Shinichiro、Igawa Satoshi、Kobayashi Makoto、Fukuda Eriko、Goshima Naoki、Ichinoe Masaaki、Jiang Shi-Xu、Satoh Yukitoshi、Masuda Noriyuki、Murakumo Yoshiki、Saegusa Makoto、Sato Yuichi
  • Journal Title: Pathology International Volume: 68 Issue: 4 Pages: 232-240
  • DOI: 10.1111/pin.12646
  • Peer Reviewed
• [Journal Article] Prognostic significance of S100A16 sub-cellular localization in lung adenocarcinoma (2018)
  • Author(s): Kobayashi Makoto、Nagashio Ryo、Saito Keita、Aguilar-Bonavides Clemente、Ryuge Shinichiro、Katono Ken、Igawa Satoshi、Tsuchiya Benio、Jiang Shi-Xu、Ichinoe Masaaki、Murakumo Yoshiki、Saegusa Makoto、Satoh Yukitoshi、Sato Yuichi
  • Journal Title: Human Pathology Volume: 74 Pages: 148-155
  • DOI: 10.1016/j.humpath.2018.01.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cytoskeleton-associated protein 4 is a novel serodiagnostic marker for lung cancer. (2018)
  • Author(s): Yanagita Kengo, Nagashio Ryo, Jiang Shi-Xu, Kuchitsu Yuki, Hachimura Kazuo, Ichinoe Masaaki, Igawa Satoshi, Fukuda Eriko, Goshima Naoki, Satoh Yukitoshi, Murakumo Yoshiki, Saegusa Makoto, Sato Yuichi.
  • Journal Title: American Journal of Pathology Volume: 188 Issue: 6 Pages: 1328-1333
  • DOI: 10.1016/j.ajpath.2018.03.007
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic significance of S100A16 subcellular localization in lung adenocarcinoma. (2018)
  • Author(s): Kobayashi Makoto, Nagashio Ryo, Saito Keita, Aguilar-Bonavides Clemente, Ryuge Shinichiro, Katono Ken, Igawa Satoshi, Tsuchiya Benio, Jiang Shi-Xu, Ichinoe Masaaki, Murakumo Yoshiki, Saegusa Makoto, Satoh Yukitoshi, Sato Yuichi.
  • Journal Title: Human Pathology Volume: 74 Pages: 148-155
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinicopathological Significance of S100A14 Expression in Lung Adenocarcinoma (2017)
  • Author(s): Katono Ken、Sato Yuichi、Kobayashi Makoto、Saito Keita、Nagashio Ryo、Ryuge Shinichiro、Igawa Satoshi、Nakashima Hiroyasu、Shiomi Kazu、Satoh Yukitoshi、Ichinoe Masaaki、Murakumo Yoshiki、Saegusa Makoto、Masuda Noriyuki
  • Journal Title: Oncology Research and Treatment Volume: 40 Issue: 10 Pages: 594-602
  • DOI: 10.1159/000478100
  • Peer Reviewed / Open Access
• [Journal Article] S100A16, a promising candidate as a prognostic marker for platinum-based adjuvant chemotherapy in resected lung adenocarcinoma (2017)
  • Author(s): Katono Ken、Sato Yuichi、Kobayashi Makoto、Nagashio Ryo、Ryuge Shinichiro、Igawa Satoshi、Ichinoe Masaaki、Murakumo Yoshiki、Saegusa Makoto、Masuda Noriyuki
  • Journal Title: OncoTargets and Therapy Volume: 10 Pages: 5273-5279
  • DOI: 10.2147/ott.s145072
  • Peer Reviewed / Open Access
• [Journal Article] Impact of PD-L1 Expression in Patients with Surgically Resected Non-Small-Cell Lung Cancer. (2017)
  • Author(s): Igawa S, Sato Y, Ryuge S, Ichinoe M, Katono K, Hiyoshi Y, Otani S, Nagashio R, Nakashima H, Katagiri M, Sasaki J, Murakumo Y, Satoh Y, Masuda N
  • Journal Title: Oncology Volume: 92 Issue: 5 Pages: 283-290
  • DOI: 10.1159/000458412
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic significance of nestin expression in patients with resected non-small cell lung cancer treated with platinum-based adjuvant chemotherapy; relationship between nestin expression and epithelial to mesenchymal transition related markers. (2017)
  • Author(s): Ryuge S, Sato Y, Nagashio R, Hiyoshi Y, Katono K, Igawa S, Nakashima H, Shiomi K, Ichinoe M, Murakumo Y, Saegusa M, Satoh Y, Masuda N
  • Journal Title: PLoS One Volume: 12 Issue: 3 Pages: e0173886-e0173886
  • DOI: 10.1371/journal.pone.0173886
  • Peer Reviewed / Open Access
• [Journal Article] Application of markers obtained by various proteomic methods to resected non-small cell lung cancer treated with platinum-based adjuvant chemotherapy (2017)
  • Author(s): 佐藤 雄一、長塩 亮、柳田 憲吾、萩生田 大介、朽津 有紀、井上 航
  • Journal Title: Electrophoresis Letters Volume: 61 Issue: 2 Pages: 128-131
  • DOI: 10.2198/electroph.61.128
  • NAID: 130006207328
  • ISSN: 2189-2628, 2189-2636
  • Peer Reviewed
• [Presentation] ランダム免疫法と免疫組織化学的スクリーニング法による腫瘍マーカー候補タンパク質の獲得 (2019)
  • Author(s): 佐藤 雄一
  • Organizer: 第60回日本組織細胞化学会
  • Invited
• [Presentation] 肺腺癌における上皮－間葉移行を標的とした血清診断マーカーの獲得 (2019)
  • Author(s): 土屋紅緒、栁田憲吾、紺野 亮、小寺義男、佐藤雄一
  • Organizer: 日本プロテオーム学会2019年大会・第70回日本電気泳動学会総会合同大会
• [Presentation] 肺腺癌におけるTRAP1の術後補助化学療法の治療効果予測マーカーとしての有用性評価 (2019)
  • Author(s): 朽津有紀、長塩 亮、井川 聡、土屋紅緒、佐藤雄一
  • Organizer: 日本プロテオーム学会2019年大会・第70回日本電気泳動学会総会合同大会
• [Presentation] S-2２ 各種プロテオーム手法で獲得したマーカーの非小細胞性肺癌における術後補助化学療法への応用 (2017)
  • Author(s): 佐藤雄一
  • Organizer: 第68回日本電気泳動学会総会
  • Invited
• [Presentation] S-20 肺癌における細胞膜タンパク質同定と血清診断マーカーとしての有用性の検討 (2017)
  • Author(s): 柳田憲吾、萩生田大介、朽津有紀、井上航、井川聡、龍華慎一郎、三枝信、長塩亮、鉢村和男、佐藤雄一
  • Organizer: 第68回日本電気泳動学会総会
  • Invited
• [Presentation] P-9 肺癌患者における術後補助化学療法の治療効果予測マーカーの探索 (2017)
  • Author(s): 朽津有紀、柳田憲吾、萩生田大介、井上航、鉢村和男、長塩亮、佐藤雄一
  • Organizer: 第68回日本電気泳動学会総会
• [Remarks] 北里大学研究者情報
  • URL: https://kerid-db.kitasato-u.ac.jp/scripts/websearch/index.htm?lang=ja
• [Remarks] 北里大学研究者情報
  • URL: http://kerid-web.kitasato-u.ac.jp/scripts/websearch/index.htm?lang=ja
• [Patent(Industrial Property Rights)] ヒト微乳頭肺腺癌細胞株及び該ヒト微乳頭肺腺癌細胞株を移植した非ヒト哺乳動物 (2017)
  • Inventor(s): 佐藤雄一、鉢村和男、長塩 亮、蒋 世旭、三枝 信、佐藤之俊
  • Industrial Property Rights Holder: 佐藤雄一、鉢村和男、長塩 亮、蒋 世旭、三枝 信、佐藤之俊
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017
  • Acquisition Date: 2019