Development of SEREX-Ag targeting antibody panel for gastric cancer

• Project/Area Number: 15K10117
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Toho University
• Principal Investigator: YAJIMA Satoshi 東邦大学, 医学部, 講師 (00408931)
• Co-Investigator(Kenkyū-buntansha): 島田 英昭 東邦大学, 医学部, 教授 (20292691) ; 根本 哲生 東邦大学, 医学部, 准教授 (70242203) ; 名波 竜規 東邦大学, 医学部, 助教 (90385831)
• Project Period (FY): 2015-04-01 – 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 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 胃癌 / 腫瘍マーカー / 抗体型腫瘍マーカー / ELISA / SEREX / HSP70 / KM-HN-1 / NY-ESO-1 / p53 / ＥＬＩＳＡ / ＳＥＲＥＸ

Outline of Final Research Achievements

Although HSP70 antibody showed similar positive rate as p53 antibody, KM-HN-1 antibody was only a half the positive rate of p53 antibody. Immunohistochemical staining for HSP70 showed a correlation with clinicopathological factors, and there was no statistically significant difference.The prognosis of the patients tended to be poor in immunostaining positive cases. With respect to KM-HN-1, the immunohistochemical characteristics are less clear. According to a recent report, an immune checkpoint inhibitor has a high therapeutic effect in autoantibody-positive cases.

Academic Significance and Societal Importance of the Research Achievements

複数の抗体を併用する方法を開発した。我々が実用化したこれらの自己抗体解析ELISAキットを用いて、免疫チェックポイント阻害剤による治療を行った症例の治療効果や予後を解析することで、これらの自己抗体の意義を明らかとする予定である。

Research Products

• [Journal Article] Prognostic impact of p53 and/or NY-ESO-1 autoantibody induction in patients with gastroenterological cancers (2020)
  • Author(s): Hoshino Isamu、Nabeya Yoshihiro、Takiguchi Nobuhiro、Gunji Hisashi、Ishige Fumitaka、Iwatate Yosuke、Shiratori Fumiaki、Yajima Satoshi、Okada Rei、Shimada Hideaki
  • Journal Title: Annals of Gastroenterological Surgery Volume: 110 Issue: 3 Pages: 2004-2013
  • DOI: 10.1002/ags3.12325
  • Peer Reviewed / Open Access
• [Journal Article] Diagnostic and prognostic impacts of six autoantibodies against multiple tumor-associated antigens with hepatocellular carcinoma. (2019)
  • Author(s): Okada R, Hoshino I, Nabeya Y, Yokoi S, Kuwajima A, Tagawa M, Matsushita K, Otsuka Y, Shimada H
  • Journal Title: Toho Journal of Medicine Volume: 5 Pages: 93-100
  • NAID: 120006733004
  • Peer Reviewed
• [Journal Article] Thymidine Phosphorylase Expression in Gastric Cancer Tissues is Associated with Thrombocytosis but not with Serum Thymidine Phosphorylase Concentration. (2018)
  • Author(s): Kikuchi Yoshinori、Ito Masaaki、Nemoto Tetsuo、Yajima Satoshi、Shiozawa Kazue、Suzuki Takashi、Oshima Yoko、Nanami Tatsuki、Watanabe Manabu、Igarashi Yoshinori、Shimada Hideaki
  • Journal Title: Toho Journal of Medicine Volume: 4 Pages: 66-73
  • NAID: 120006523344
  • Peer Reviewed
• [Journal Article] Is high serum programmed death ligand 1 level a risk factor for poor survival in patients with gastric cancer? (2018)
  • Author(s): Ito Masaaki、Oshima Yoko、Yajima Satoshi、Suzuki Takashi、Nanami Tatsuki、Shiratori Fumiaki、Funahashi Kimihiko、Nemoto Tetsuo、Shimada Hideaki
  • Journal Title: Annals of Gastroenterological Surgery Volume: 2 Issue: 4 Pages: 313-318
  • DOI: 10.1002/ags3.12175
  • Peer Reviewed
• [Journal Article] Five-year postsurgical monitoring of serum p53 antibody for locally advanced esophageal squamous cell carcinoma (2018)
  • Author(s): Kochi Ryosuke、Yajima Satoshi、Nanami Tatsuki、Suzuki Takashi、Oshima Yoko、Tokura Natsuki、Takatsuka Jun、Funahashi Kimihiko、Tochigi Naobumi、Shimada Hideaki
  • Journal Title: Clinical Journal of Gastroenterology Volume: 11 Issue: 4 Pages: 278-281
  • DOI: 10.1007/s12328-018-0839-3
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic significance of high serum p53 antibody titers in patients with esophageal squamous cell carcinoma (2018)
  • Author(s): Suzuki Takashi、Yajima Satoshi、Ishioka Nobuki、Nanami Tatsuki、Oshima Yoko、Washizawa Naohiro、Funahashi Kimihiko、Otsuka Seiko、Nemoto Tetsuo、Shimada Hideaki
  • Journal Title: Esophagus Volume: 15 Issue: 4 Pages: 294-300
  • DOI: 10.1007/s10388-018-0629-5
  • NAID: 40021670369
  • Peer Reviewed
• [Journal Article] Clinicopathological significance of serum NY-ESO-1 antibodies in patients with gastric cancer. (2017)
  • Author(s): Yajima Satoshi、Shimada Hideaki、Nemoto Tetsuo、Ito Masaaki、Suzuki Takashi、Nanami Tatsuki、Oshima Yoko、Shiratori Fumiaki、Kuwajima Akiko、Kaneko Hironori
  • Journal Title: Toho Journal of Medicine Volume: 3 Pages: 101-106
  • NAID: 120006422779
  • Peer Reviewed / Open Access
• [Journal Article] Negative conversion of high serum p53 antibody titers in a patient with gastric cancer at 31 months after surgery (2017)
  • Author(s): Murayama Kenji、Nanami Tatsuki、Suzuki Takashi、Oshima Yoko、Yajima Satoshi、Nemoto Tetsuo、Shimada Hideaki
  • Journal Title: Clinical Journal of Gastroenterology Volume: 10 Issue: 4 Pages: 357-360
  • DOI: 10.1007/s12328-017-0749-9
  • Peer Reviewed / Open Access
• [Journal Article] A panel of autoantibodies against multiple tumor-associated antigens for detecting gastric cancer (2017)
  • Author(s): Hoshino, I., Nagata, M., Takiguchi, N., Nabeya, Y., Ikeda, A., Yokoi, S., Kuwajima, A., Tagawa, M., Matsushita, K., Yajima, S., Shimada, H.
  • Journal Title: Cancer Sci Volume: 108 Issue: 3 Pages: 308-315
  • DOI: 10.1111/cas.13158
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Hyperfibrinogenemia is associated with inflammatory mediators and poor prognosis in patients with gastric cancer. (2016)
  • Author(s): Suzuki Takashi, Shimada H, Nanami T, Oshima Y, Yajima S, Ito M, Washizawa N, Kaneko H
  • Journal Title: Surgery today Volume: 46(12) Issue: 12 Pages: 1394-1401
  • DOI: 10.1007/s00595-016-1339-z
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] NY-ESO-1 autoantibody as a tumor-specific biomarker for esophageal cancer: screening in 1969 patients with various cancers.(Erratum to: NY-ESO-1 autoantibody as a tumor-specific biomarker for esophageal cancer: screening in 1969 patients with various cancers.） (2016)
  • Author(s): Oshima Y, Shimada H, Yajima S, Nanami T, Matsushita K, Nomura F, Kainuma O, Takiguchi N, Soda H, Ueda T, Iizasa T, Yamamoto N, Yamamoto H, Nagata M, Yokoi S, Tagawa M, Otsuka S†, Kuwajima A, Murakami A, Kaneko H
  • Journal Title: Journal of gastroenterology Volume: 51-1 Issue: 1 Pages: 30-34
  • DOI: 10.1007/s00535-015-1089-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 【胃癌の診療】胃癌診断における腫瘍マーカーの臨床的意義. (2015)
  • Author(s): 大嶋陽幸, 名波竜規, 鈴木 隆, 谷島 聡, 島田英昭
  • Journal Title: 臨床消化器内科 Volume: 30-7 Pages: 806-809
• [Presentation] 食道扁平上皮癌における血清ミドカインの検討. (2019)
  • Author(s): 白鳥史明, 伊藤正朗, 谷島 聡, 鈴木 隆, 大嶋陽幸, 名波竜規, 船橋公彦, 島田英昭
  • Organizer: 第119回日本外科学会定期学術集会
• [Presentation] Presence of serum autoantibodies against Ras-like GTPases, RalA, in patients with gastric cancer. (2019)
  • Author(s): Shimada Hideaki, Nanami Tatsuki, Yajima Satoshi, Oshima Yoko, Ito Masaaki, Suzuki Takashi, Funahashi Kimihiko, Nabeya Yoshihiro, Tagawa Masatoshi, Matsushita Kazuyuki, Hoshino Isamu
  • Organizer: 13th International Gastric Cancer Congres(IGCC 2019)
  • Int'l Joint Research
• [Presentation] 胃癌患者における血清RalA 抗体の臨床病理学的検討. (2018)
  • Author(s): 名波竜規, 島田英昭, 白鳥史明, 鈴木 隆, 大嶋陽幸, 谷島 聡, 大塚由一郎, 鷲澤尚宏, 船橋公彦
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] 胃癌手術症例における血清p53 抗体価の意義（CEA，CA19-9 との比較）. (2018)
  • Author(s): 大嶋陽幸, 栗原奈津子, 石岡伸規, 吉野 優, 長嶋康雄, 鈴木 隆, 名波竜規, 谷島 聡, 大塚由一郎, 船橋公彦, 島田英昭
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] 血清PD-L1 は胃癌予後因子となるか？. (2018)
  • Author(s): 伊藤正朗, 大嶋陽幸, 谷島 聡, 鈴木 隆, 名波竜規, 白鳥史明, 大塚由一郎, 船橋公彦, 根本哲生, 島田英昭
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] 食道癌扁平上皮癌における血清SCC 抗原値の基準値と予後との関係について. (2018)
  • Author(s): 石岡伸規, 鈴木 隆, 谷島 聡, 大島陽幸, 名波竜規, 大塚由一郎, 船橋公彦, 島田英昭
  • Organizer: 第118回日本外科学会定期学術集会
• [Presentation] 胃癌におけるTYMP の血清値と病理学的発現との検討. (2017)
  • Author(s): ◎菊池由宣†, 伊藤正朗†, 根本哲生†, 谷島 聡†, 塩澤一惠†, 名波竜規†, 鈴木 隆†, 大嶋陽幸†, 渡邉 学†, 五十嵐良典†, 住野泰清†, 島田英昭†
  • Organizer: 第89回日本胃癌学会総会
  • Place of Presentation: 広島国際会議場(広島県広島市)
  • Year and Date: 2017-03-10
• [Presentation] Prognostic significance of serum p53 autoantibodies in the patients with pT1N0 esophageal carcinoma. (2017)
  • Author(s): Ishioka Nobuki, Suzuki Takashi, Nanami Tatsuki, Oshima Yoko, Yajima Satoshi, Funahashi Kimihiko, Kaneko Hironori, Shimada Hideaki
  • Organizer: IASGO-CME Advanced Post-Graduate Course in Yokohama 2017
  • Int'l Joint Research
• [Presentation] 胃癌におけるHeat shock protein 70（HSP70）発現と臨床病理学的検討～新規胃癌バイオマーカー開発を目指して～. (2017)
  • Author(s): 谷島 聡, 島田英昭, 名波竜規, 鈴木 隆, 伊藤正朗, 大嶋陽幸, 白鳥史明, 岡田 嶺, 須磨崎真, 根本哲生, 金子弘真
  • Organizer: 第117回日本外科学会定期学術集会
• [Presentation] 胃癌患者における血清自己抗体（RalA，NY-ESO-1，p53）の解析. (2017)
  • Author(s): 名波竜規, 島田英昭, 白鳥史明, 鈴木 隆, 大嶋陽幸, 谷島 聡, 鷲澤尚宏, 金子弘真
  • Organizer: 第117回日本外科学会定期学術集会
• [Presentation] 消化管癌における血清p53抗体の有用性と今後の展望. (2016)
  • Author(s): ◎谷島 聡†, 島田英昭†, 鈴木 隆†, 大嶋陽幸†, 名波竜規†, 鈴木孝之†, 牛込充則†, 小池淳一†, 船橋公彦†, 金子弘真†
  • Organizer: 第14回日本消化器外科学会大会（JDDW2016）
  • Place of Presentation: 神戸コンベンションセンター(兵庫県神戸市)
  • Year and Date: 2016-11-05
• [Presentation] Is Tissue Microarray Appropriate to Evaluate NY-ESO-1 Antigen Expression in Patients with Gastric Cancer? -Comparative Study with Serum NY-ESO-1 antibodies-. (2016)
  • Author(s): Yajima S†, Shimada H†, Suzuki Takashi†, Nanami T†, Oshima Y†, Ito M†, Nemoto T†, Kaneko H†
  • Organizer: 40th World Congress of the International College of Surgeons(ICS Kyoto 2016)
  • Place of Presentation: 京都国際会議場（京都府京都市）
  • Year and Date: 2016-10-25
  • Int'l Joint Research
• [Presentation] 胃癌患者における血清NYESO-1抗体の解析. (2016)
  • Author(s): 谷島聡, 島田英昭
  • Organizer: 第13回日本免疫治療学研究会
  • Place of Presentation: 東京ガーデンパレス湯島会館（東京都文京区）
  • Year and Date: 2016-02-02
• [Presentation] 胃癌手術症例におけるNY-ESO-1血清抗体および免疫染色による臨床病理学的検討. (2015)
  • Author(s): 谷島聡, 鈴木隆
  • Organizer: 第69回東邦医学会総会
  • Place of Presentation: 東邦大学（東京都大田区）
  • Year and Date: 2015-11-01
• [Presentation] 胃癌患者におけるheat shock protein 70, KM-HN-1, p53 抗原を標的とした血清抗体の検出. (2015)
  • Author(s): 谷島 聡, 島田英昭, 伊藤正朗, 鈴木 隆, 名波竜規, 大嶋陽幸, 鷲澤尚宏, 金子弘真
  • Organizer: 第35回日本分子腫瘍マーカー研究会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-07
• [Presentation] 新規胃癌バイオマーカーとしての血清p53 抗体と組織アレイを用いた免疫染色の意義. (2015)
  • Author(s): 谷島聡, 島田英昭, 澤口悠子, 松本 悠, 竹山照明, 鈴木 隆, 名波竜規, 大嶋陽幸, 鷲澤尚宏, 根本哲生, 金子弘真
  • Organizer: 第115回日本外科学会定期学術集会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-18
• [Presentation] 胃癌症例における腫瘍抗原特異的血清抗体診断の開発. (2015)
  • Author(s): 島田英昭, 谷島 聡, 大嶋陽幸, 名波竜規, 鈴木 隆, 鷲澤尚宏, 大塚誠子, 船橋公彦, 金子弘真
  • Organizer: 第115回日本外科学会定期学術集会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-18
• [Book] 分子腫瘍マーカー診療ガイドライン (2016)
  • Author(s): 大嶋陽幸†, 谷島聡†, 名波竜規†, 鈴木隆†, 島田英昭†
  • Publisher: 金原出版
• [Book] 日常診療のための検査値のみかた. (2015)
  • Author(s): 谷島 聡, 島田英昭
  • Total Pages: 2
  • Publisher: 中外医学社