The Clinicopathological Signficance of Serum RalA Autoantibody in the Patients with Gastric Cancer

• Project/Area Number: 16K10519
• 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: NANAMI Tatsuki 東邦大学, 医学部, 助教 (90385831)
• Co-Investigator(Kenkyū-buntansha): 島田 英昭 東邦大学, 医学部, 教授 (20292691) ; 大嶋 陽幸 東邦大学, 医学部, 助教 (00424705)
• Project Period (FY): 2016-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: SEREX / RalA / 胃癌 / 血清抗体 / 腫瘍マーカー / ＥＬＩＳＡ / ＲａｌＡ

Outline of Final Research Achievements

Serum antibody levels were measured using peroxidase-labeled anti-human IgG antibodies and the most antigenic epitope was selected. The positive rate of RalA antibody in gastric cancer cases was calculated using the average + 2SD of the healthy control group as a reference value. Overall positive rate of RalA antibody was 15%. We investigated the correlation between the presence of serum RalA and TNM factors. No significant associations were observed. We also examined the correlation with recurrence time and prognosis. Again, no significant association was observed. RalA antibody and p53 antibody were complementary, and the combined use significantly increased the positive rate. Looking at the prognosis when used in combination with CEA / CA19-9, it was found that the prognosis was significantly poor when all three serum markers were positive.

Academic Significance and Societal Importance of the Research Achievements

当初計画に基づき胃癌におけるRALA抗体の臨床病理学的意義を明らかとして、予後との関連性について解析した。RALA抗体単独での陽性率は１５％と高くはないが、既存のCEA/CA19-9とは独立して陽性となるため補完的な腫瘍マーカーとして有用と思われた。予後への影響は限定的ではあるが、CEA/CA19-9と併用することで、予後不良症例を選別することが可能であることが示唆された。

Research Products

• [Journal Article] Prevalence of serum galectin?1 autoantibodies in seven types of cancer: A potential biomarker (2021)
  • Author(s): Nanami Tatsuki、Hoshino Isamu、Shiratori Fumiaki、Yajima Satoshi、Oshima Yoko、Suzuki Takashi、Ito Masaaki、Hiwasa Takaki、Kuwajima Akiko、Shimada Hideaki
  • Journal Title: Molecular and Clinical Oncology Volume: 15 Issue: 3 Pages: 179-179
  • DOI: 10.3892/mco.2021.2341
  • Peer Reviewed
• [Journal Article] Identification of serum anti?striatin 4 antibodies as a common marker for esophageal cancer and other solid cancers (2021)
  • Author(s): Ito Masaaki、Hiwasa Takaki、Oshima Yoko、Yajima Satoshi、Suzuki Takashi、Nanami Tatsuki、Sumazaki Makoto、Shiratori Fumiaki、Funahashi Kimihiko、Takizawa Hirotaka、Kashiwado Koichi、Tochigi Naobumi、Shimada Hideaki
  • Journal Title: Molecular and Clinical Oncology Volume: 15 Issue: 5 Pages: 237-237
  • DOI: 10.3892/mco.2021.2399
  • Peer Reviewed
• [Journal Article] Prevalence of autoantibodies against Ras?like GTPases, RalA, in patients with gastric cancer (2020)
  • Author(s): Nanami Tatsuki、Hoshino Isamu、Ito Masaaki、Yajima Satoshi、Oshima Yoko、Suzuki Takashi、Shiratori Fumiaki、Nabeya Yoshihiro、Funahashi Kimihiko、Shimada Hideaki
  • Journal Title: Molecular and Clinical Oncology Volume: 13
  • DOI: 10.3892/mco.2020.2098
  • Peer Reviewed / Open Access
• [Journal Article] Identification of specific and common diagnostic antibody markers for gastrointestinal cancers by SEREX screening using testis cDNA phage library (2018)
  • Author(s): Kobayashi Sohei、Hiwasa Takaki、Arasawa Takahiro、Kagaya Akiko、Ishii Sayaka、Shimada Hideaki、Ito Masaaki、Suzuki Masae、Kano Masayuki、Rahmutulla Bahityar、Kitamura Kouichi、Sawabe Yuji、Shin Hideo、Takiguchi Masaki、Nomura Fumio、Matsubara Hisahiro、Matsushita Kazuyuki
  • Journal Title: Oncotarget Volume: 9 Issue: 26 Pages: 18559-18569
  • DOI: 10.18632/oncotarget.24963
  • Peer Reviewed / Open Access
• [Journal Article] Prospective pilot study of adoptive immunotherapy with autologous αβT cells for five cases of advanced and/or recurrent esophageal squamous cell carcinoma (2017)
  • Author(s): Nanami Tatsuki、Shimada Hideaki、Yajima Satoshi、Oshima Yoko、Suzuki Takashi、Shiratori Fumiaki、Sumazaki Makoto、Otsuka Seiko、Kamigaki Takashi、Goto Shigenori、Kaneko Hironori
  • Journal Title: Esophagus Volume: 14 Issue: 4 Pages: 303-308
  • DOI: 10.1007/s10388-017-0577-5
  • NAID: 40021339454
  • Peer Reviewed
• [Journal Article] Presence of Autoantibodies against Ras-like GTPases in Serum in Stage I/II Breast Cancer. (2017)
  • Author(s): Kubota Yorichika、Ogata Hideaki、Otsuka Seiko、Kuwajima Akiko、Saito Fumi、Shimada Hideaki
  • Journal Title: Toho J Med Volume: 3 Pages: 125-130
  • NAID: 120006422782
  • Peer Reviewed
• [Journal Article] Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin. (2017)
  • Author(s): Ak G, Tada Y, Shimada H†, Metintas S, Ito M, Hiroshima K, Tagawa M, Metintas M
  • Journal Title: BMC cancer Volume: 17（1） Issue: 1 Pages: 212-212
  • DOI: 10.1186/s12885-017-3209-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical significance of serum autoantibodies against Ras-like GTPases, RalA, in patients with esophageal squamous cell carcinoma. (2016)
  • Author(s): Nanami, T., Shimada, H., Yajima, S., Oshima, Y., Matsushita, K., Nomura, F., Nagata, M., Tagawa, M., Otsuka, S., Kuwajima, A. and Kaneko, H
  • Journal Title: Esophagus Volume: 13 Issue: 2 Pages: 167-172
  • DOI: 10.1007/s10388-015-0510-8
  • NAID: 40020807867
  • Peer Reviewed / Open Access
• [Presentation] 腫瘍抗原を標的とする胃癌新規抗体マーカーのスクリーニング. (2021)
  • Author(s): 谷島 聡, 伊藤正朗, 名波竜規, 白鳥史明, 鈴木 隆, 大嶋陽幸, 大塚由一郎, 船橋公彦, 日和佐隆樹, 島田英昭
  • Organizer: 第121回日本外科学会定期学術集会
• [Presentation] 複数の癌腫842 例における血清RalA 抗体と血清p53 抗体の検討. (2021)
  • Author(s): 名波竜規, 星野敢, 白鳥史明, 鈴木隆, 大嶋陽幸, 谷島聡, 船橋公彦, 島田英昭
  • Organizer: 第76回日本消化器外科学会総会
• [Presentation] 術前抗p53 抗体陽性胃癌症例の術後抗体価の推移の検討(続報). (2021)
  • Author(s): 大嶋陽幸, 白鳥史明, 名波竜規, 鈴木 隆, 谷島 聡, 船橋公彦, 島田英昭
  • Organizer: 第76回日本消化器外科学会総会
• [Presentation] 胃癌手術症例における血清抗SOHLH1 抗体の解析. (2021)
  • Author(s): 谷島聡, 伊藤正朗, 白鳥史明, 名波竜規, 大嶋陽幸, 鈴木 隆, 大塚由一郎, 船橋公彦, 日和佐隆樹, 島田英昭
  • Organizer: 第76回日本消化器外科学会総会
• [Presentation] 胃癌および他の消化器癌の患者における自己抗体誘導および遺伝子発現の予後の影響. (2021)
  • Author(s): 山崎信人, 大嶋陽幸, 白鳥史明, 酒井隆光, 鏡 哲, 名波竜規, 鈴木 隆, 谷島 聡, 船橋公彦, 島田英昭
  • Organizer: 第93回日本胃癌学会総会
• [Presentation] 抗p53抗体価100以上の胃癌手術症例は予後が悪い. (2021)
  • Author(s): 大嶋陽幸, 白鳥史明, 名波竜規, 鈴木 隆, 谷島 聡, 島田英昭
  • Organizer: 第93回日本胃癌学会総会
• [Presentation] 胃癌手術症例における血清p53 抗体価の予後因子としての意義. (2020)
  • Author(s): 大嶋陽幸, 名波竜規, 鈴木 隆, 谷島 聡, 船橋公彦, 島田英昭
  • Organizer: 第75回日本消化器外科学会総会
• [Presentation] 胃癌手術症例における術後血清亜鉛値の推移. (2020)
  • Author(s): 大嶋陽幸, 白鳥史明, 名波竜規, 鈴木 隆, 谷島 聡, 島田英昭
  • Organizer: 第92回日本胃癌学会総会
• [Presentation] Presence of serum autoantibodies against Ras-like GTPases, RalA, in patients with gastric cancer. (2019)
  • Author(s): Shimada H, Nanami T, Yajima S, Oshima Y, Ito M, Suzuki T, Funahashi K, Nabeya Y, Tagawa M, Matsushita K, Hoshino I
  • 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] 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] 胃癌切除症例における血清p53 抗体価の推移の評価方法について. (2017)
  • Author(s): 大嶋陽幸, 島田英昭, 白鳥史明, 澤口悠子, 三浦康之, 鈴木 隆, 名波竜規, 谷島 聡, 金子弘真
  • Organizer: 第117回日本外科学会定期学術集会
• [Presentation] 胃癌・食道癌手術症例における抗TIF1-γ抗体の検討. (2017)
  • Author(s): 須磨崎真, 伊藤正朗, 澤口悠子, 名波竜規, 鈴木 隆, 大嶋陽幸, 谷島 聡, 船橋公彦, 島田英昭
  • Organizer: 第72回日本消化器外科学会総会
• [Presentation] 胃癌・食道癌手術症例における抗TIF1-γ抗体の検討. (2017)
  • Author(s): 須磨崎真, 伊藤正朗, 澤口悠子, 名波竜規, 鈴木 隆, 大嶋陽幸, 谷島 聡, 船橋公彦, 島田英昭
  • Organizer: 第15回日本消化器外科学会大会（JDDW2017）
• [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: 第40回国際外科学会世界総会(ICS Kyoto 2016)
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-10-25
  • Int'l Joint Research
• [Presentation] Useful serum biomarkers in pretreatment staging of esophageal cancer. (2016)
  • Author(s): Shimada H, Yajima S, Suzuki Takashi, Oshima Y, Nanami T, Shiratori F, Kaneko H
  • Organizer: The 15th World Congress of the International Society for Diseases of the Esophagus(ISDE 2016)
  • Place of Presentation: Singapore(Singapore)
  • Year and Date: 2016-09-20
  • Int'l Joint Research
• [Presentation] Serum p53-antibody positive esophageal Squamous cell carcinoma had a low sensitivity to chemotherapy. (2016)
  • Author(s): Yajima S, Shimada H, Suzuki Takashi, Nanami T, Oshima Y, Ito M, Nemoto T, Kaneko H
  • Organizer: The 15th World Congress of the International Society for Diseases of the Esophagus(ISDE 2016)
  • Place of Presentation: Singapore(Singapore)
  • Year and Date: 2016-09-19
  • Int'l Joint Research
• [Presentation] 食道癌・胃癌における新規自己抗体である血清RalA 抗体の解析. (2016)
  • Author(s): 名波竜規, 島田英昭, 白鳥史明, 松本 悠, 三浦康之, 竹山照明, 鈴木 隆, 大嶋陽幸, 谷島 聡, 鷲澤尚宏, 根本哲生, 金子弘真
  • Organizer: 第116回日本外科学会定期学術集会
  • Place of Presentation: リーガロイヤルホテル大阪(大阪府大阪市)
  • Year and Date: 2016-04-15