Development of a novel glycoprotein serum biomarker for epithelial ovarian cancer with more superior diagnostic capability than CA125

2016 Fiscal Year Annual Research Report

• Project/Area Number: 26462538
• Research Institution: Tokai University
• Principal Investigator: 三上 幹男 東海大学, 医学部, 教授 (30190606)
• Co-Investigator(Kenkyū-buntansha): 岩森 正男 近畿大学, 理工学部, 教授 (90110022) ; 池田 仁惠 東海大学, 医学部, 講師 (20365993)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: バイオマーカー / 卵巣明細胞腺癌 / 子宮内膜症性嚢胞 / C4 binding proein / フルシアル化 / CA125 / 糖脂質 / GM2

Outline of Annual Research Achievements

1.昨年度に我々は、血清糖蛋白を糖ペプチドに分解後、LC/MSを用いて網羅的に分析する方法（網羅的血清糖ペプチドプロファイル解析）にて、子宮内膜症性嚢胞（EM）の経過観察に用いることで明細胞腺癌（CCC）早期診断に有用な可能性のある新規卵巣癌の糖ペプチドバイオマーカーA2160を同定した。A2160はcomplement-4 binding protein（C4BP）のα鎖のフルシアル化された糖ペプチドであった。A2160測定系の簡便化のためのA2160糖ペプチドのフルシアル化の割合をみる測定系の開発（FS-C4BP Index）、及び血清フルC4BPとA2160とのCombination Assay(COMB)によるマーカーとしての感度特異度の向上を目指した。FS-C4BP IndexはEMとCCCの鑑別においてA2160と同等の感度特異度を示し測定系の簡便化が可能であった。またCOMBではA2160単独よりも高い特異度を示した。今後さらなる感度・特異度向上のために、健常人群、良性群と卵巣癌群の網羅的血清糖ペプチドプロファイル解析にて得られた各群で有意差のある糖ペプチド全ピークを用いたEMとCCCの鑑別を行う診断システム、健常人と卵巣癌例の鑑別を行う診断システムの開発を目指す。
2.我々はすでにsulfatideが黄体期正常子宮内膜及び低分化型と比べて高分化型子宮類内膜腺癌で発現増強することを報告している。今回移植腫瘍にて低分化形態を示す類内膜癌培養細胞株に硫酸基転移酵素遺伝子を導入し移植腫瘍を作成したところ高分化の形態を示すことが判明した。つまり子宮類内膜腺癌の分化度にはsulfatide発現が関与していることが明らかになった。今後はsulfatideに関しての子宮体癌の分化機構の解明を分化誘導療法の解明につなげていきたい。

Research Products

• [Journal Article] Effective Selection of a Well-Differentiated Type of Human Uterine Endometrial Carcinoma Cells by Transfection of the Sulfotransferase Gene and Possible Association of Sulfoglycolipids With Well-Differentiated Phenotypes. (2017)
  • Author(s): K Tanaka, I Ishiwata, K Kubushiro, M Mikami, D Aoki, K Kiguchi, and M Iwamori
  • Journal Title: International Journal of Gynecological Cancer Volume: 27(2) Pages: 267-273
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Randomized Phase III Trial of Irinotecan Plus Cisplatin Compared With Paclitaxel Plus Carboplatin As First-Line Chemotherapy for Ovarian Clear Cell Carcinoma: JGOG3017/GCIG Trial. (2016)
  • Author(s): Sugiyama T, Okamoto A, Enomoto T, Hamano T, Aotani E, Terao Y, Suzuki N, Mikami M, Yaegashi N, Kato K, Yoshikawa H, Yokoyama Y, Tanabe H, Nishino K, Nomura H, Kim JW, Kim BG, Pignata S, Alexandre J, Green J, Isonishi S, Terauchi F, Fujiwara K, Aoki D.
  • Journal Title: Journal of Clinical Oncology Volume: 34(24) Pages: 2881-2887
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association of Low-Dose Aspirin and Survival of Women With Endometrial Cancer. (2016)
  • Author(s): Matsuo K, Cahoon SS, Yoshihara K, Shida M, Kakuda M, Adachi S, Moeini A, Machida H, Garcia-Sayre J, Ueda Y, Enomoto T, Mikami M, Roman LD, Sood AK
  • Journal Title: Obstet Gynecol Volume: 128(1) Pages: 127-137
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Enhanced expression of unique gangliosides with GM2-determinant in human uterine cervical carcinoma-derived cell lines. (2016)
  • Author(s): Tanaka K, Miyazawa M, Mikami M, Aoki D, Kiguchi K, Iwamori M.
  • Journal Title: Glycoconjugate Journal Volume: 33(5) Pages: 745-754
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer. (2016)
  • Author(s): Komiyama S, Katabuchi H, Mikami M, Nagase S, Okamoto A, Ito K, Morishige K, Suzuki N, Kaneuchi M, Yaegashi N, Udagawa Y, Yoshikawa H.
  • Journal Title: International Journal of Clinical Oncology Volume: 21(3) Pages: 435-446
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Japan Society of Gynecologic Oncology guidelines 2013 for the treatment of uterine body neoplasms. (2016)
  • Author(s): Ebina Y, Katabuchi H, Mikami M, Nagase S, Yaegashi N, Udagawa Y, Kato H, Kubushiro K, Takamatsu K, Ino K, Yoshikawa H.
  • Journal Title: International Journal of Clinical Oncology Volume: 21(3) Pages: 419-434
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Practice patterns of adjuvant therapy for intermediate/high recurrence risk cervical cancer patients in Japan. (2016)
  • Author(s): Ikeda Y, Furusawa A, Kitagawa R, Tokinaga A, Ito F, Ukita M, Nomura H, Yamagami W, Tanabe H, Mikami M, Takeshima N, Yaegashi N.
  • Journal Title: Journal of Gynecologic Oncology Volume: 27(3) Pages: e29
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Use of epithelial-specific antigen for cytological diagnosis of glandular lesions in the uterine cervix. (2016)
  • Author(s): Matsui N, Kajiwara H, Morishita A, Iida T, Nakazawa K, Miyazawa M, Mikami M, Ogawa T, Nakamura N, Sato S.
  • Journal Title: Pathology International Volume: 66(5) Pages: 305-308
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma. (2016)
  • Author(s): K Matsuo, Y Takazawa, M. S.Ross, E Elishaev, I Podzielinski, M Yunokawa, T.B Sheridan, S.H.Bush, M.M.Klobocista, E.A.Blake, T Takano, S Matsuzaki, T Baba, S Satoh, M Shida, T Nishikawa, Y Ikeda, S Adachi, T Yokoyama, M Mikami et al
  • Journal Title: Annals of Oncology Volume: 27(7) Pages: 1257-1266
  • DOI: 10.1093/annonc/mdw161
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Implementation and quality assurance of training institutions for gynecologic oncologists in Japan (2017)
  • Author(s): M Mikami,M Shida,T Shibata,J Kigawa,H Katabuchi,D Aoki,H Yoshikawa,N Yaegashi
  • Organizer: SGO2017 Annual Meeting on Women's Cancer
  • Place of Presentation: Gaylord National Resort & Convention Center (アメリカ)
  • Year and Date: 2017-03-11 – 2017-03-15
  • Int'l Joint Research
• [Presentation] Comparison of adjuvant therapy for node-positive,high-risk,early-stage cervical cancer:Systemic chemotherapy vs.pelvic irradiation (2017)
  • Author(s): K Matsuo,M Shimada,Y Aoki M Sakamoto,M Mikami, H Fujiwara,N Takeshima,T Sugiyama
  • Organizer: SGO2017 Annual Meeting on Women's Cancer
  • Place of Presentation: Gaylord National Resort & Convention Center (アメリカ)
  • Year and Date: 2017-03-11 – 2017-03-15
  • Int'l Joint Research
• [Presentation] FS-C4BP (fully-sialylated alpha-chain of complement 4-binding protein) is a novel biomarker that can detect early stage epithelial ovarian cancer, especially clear cell carcinoma (2016)
  • Author(s): M Ikeda, I Oiwa, I Hayashi, T Narayama, T Iida, T Hirasawa, M Mikami
  • Organizer: 16th Biennial Meeting of the International Gynecologic Cancer Society IGCS2016
  • Place of Presentation: Lisboa Congress Centre（ポルトガル）
  • Year and Date: 2016-10-29 – 2016-10-31
  • Int'l Joint Research
• [Presentation] Ovarian cancer prevention for women at population risk ( No genetic predisposition for ovarian cancer ) (2016)
  • Author(s): M Mikami
  • Organizer: 第54回日本癌治療学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-20 – 2016-10-22
• [Presentation] Possible involvement of glycolipids in anticancer drug resistance of several ovarian carcinoma-derived cells. (2016)
  • Author(s): K Tanaka, K Kiguchi,M Mikami,D Aoki,M Iwamori
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川横浜市）
  • Year and Date: 2016-10-06 – 2016-10-08
• [Presentation] Imprint Cytological Diagnosis of Metastatic Lynphnodes During Surgery In Gynecological Cancers (2016)
  • Author(s): M Shida,M Ikeda,N Kato,Y Miyajima,H Ito,T Hirasawa,H Kajiwara,N Nakamura,M Mikami
  • Organizer: The 19th International Congress of Cytology
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-05-28 – 2016-06-01
  • Int'l Joint Research
• [Presentation] 子宮頸癌術後療法による合併症の差異-多施設共同後方視的検討結果から- (2016)
  • Author(s): 古澤啓子、喜多川亮、喜多恒和、金尾祐之、小島淳美、武隈宗孝、戸澤晃子、西尾真、山口聡、三上幹男
  • Organizer: 第68回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2016-04-21 – 2016-04-24