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

• Project/Area Number: 26462538
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Tokai University
• Principal Investigator: MIKAMI Mikio 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
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 卵巣癌 / 腫瘍マーカー / 糖蛋白質 / 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 / C4 binding protein / 子宮内膜症性卵巣嚢腫 / 糖タンパク / 抗がん剤耐性 / トランスポーター

Outline of Final Research Achievements

No useful biomarker is currently available for early detection of epithelial ovarian cancer (EOC). More than 100,000 glycopeptides of serum glycoproteins obtained from all stage EOC patients and non-cancer control women (including endometriomas: EM) were explored for a mass spectrum approach. A2160, a fully-sialylated alpha-chain of complement 4-binding protein, (C4BP) was identified. A2160 was significantly elevated in all stages of Clear cell carcinoma (CCC) patients compared to with EMs. Diagnostic accuracy of A2160 to distinguish early stage CCC from EMs is significantly higher than that of CA-125. In addition, fully-sialylated glycans had a higher accuracy for diagnosing EOC as compared to partially-sialylated glycans of C4BP. Our study suggested that A2160 may be a useful biomarker to distinguish early-stage CCC from EM. This new biomarker can be potentially applied for the monitoring of EM patients, which could make the early diagnosis of CCC possible.

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)
  • 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): Matsuo K, Takazawa Y, Ross MS, Elishaev E, Podzielinski I, Yunokawa M, Sheridan TB, Bush SH, Klobocista MM, Blake EA, Takano T, Matsuzaki S, Baba T, et al.
  • Journal Title: Ann Oncol. Volume: 27 Issue: 7 Pages: 1257-1266
  • DOI: 10.1093/annonc/mdw161
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Japan Society of Gynecologic Oncology guidelines 2011 for the treatment of uterine cervical cancer (2015)
  • Author(s): Yasuhiko Ebina, Nobuo Yaegashi, Hidetaka Katabuchi, Satoru Nagase,Yasuhiro Udagawa, Toru Hachisuga, Tsuyoshi Saito, Mikio Mikami, Yoichi Aoki,Hiroyuki Yoshikawa
  • Journal Title: International Journal of Clinical Oncology Volume: 20 Issue: 2 Pages: 240-248
  • DOI: 10.1007/s10147-015-0806-7
  • Peer Reviewed / Open Access
• [Journal Article] Fully-sialylated alpha-chain of complement 4-binding protein:Diagnostic utility for ovarian clear cell carcinoma (2015)
  • Author(s): Mikio Mikami,Kazuhiro Tanabe,Koji Matsuo,Yuko Miyazaki,Masaki Miyazawa,Masaru Hayashi,Satoshi Asai,Masae Ikeda,Masako Shida,Takeshi Hirasawa,Nozomi Kojima,Ryuichiro Sho,Sadato Iijima
  • Journal Title: Gynecologic Oncology Volume: 138(3) Issue: 3 Pages: 520-528
  • DOI: 10.1016/j.ygyno.2015.10.012
  • Peer Reviewed / Open Access
• [Journal Article] Enhanced Expression of Hydroxylated Ceramide in Well-Differentiated Endometrial adenocarcinoma (2015)
  • Author(s): Toshiki Tajima,Masaki Miyazawa,Masaru Hayashi,Satoshi Asai,Masae Ikeda,Masako Shida,Takeshi Hirasawa,Susumu Takekoshi,Masao Iwamori,Mikio Mikami
  • Journal Title: Oncology Letters Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Possible role of thymidine phosphorylase in gynecological tumors as an individualized treatment strategy (2015)
  • Author(s): Masako Shida,Masanori Yasuda,Mariko Fujita,Masaki Miyazawa,Hiroshi Kajiwara,Takeshi Hirasawa,Masae Ikeda,Naruaki Matsui,Toshinari Muramatsu,Mikio Mikami
  • Journal Title: Oncology Letters Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Clostridium botulinum type C hemagglutinin affects morphology and viability of cultured mammalian cells via binding to the ganglioside GM3. (2015)
  • Author(s): Sugawara Y, Iwamori M, Matsumura T, Yutani M, Amatsu S, Fujinaga Y.
  • Journal Title: FEBS Journal Volume: 282 Pages: 3334-3347
  • Peer Reviewed
• [Journal Article] Expression of sulfatide and sulfated lactosylceramide among histological types of human ovarian carcinomas. (2015)
  • Author(s): Tanaka K, Mikami M, Aoki D, Kiguchi K, Ishiwata I, Iwamori M.
  • Journal Title: Hum Cell Volume: 28 Issue: 1 Pages: 37-43
  • DOI: 10.1007/s13577-014-0100-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Lewis y enhances CAM-DR in ovarian cancer cells by activating the FAK signaling pathway and upregulating Bcl-2/Bcl-XL expression. (2015)
  • Author(s): Yan LM, Wang CZ, Lin B, Liu JJ, Liu DW, Hou R, Wang YF, Gao LL, Zhang SL, Iwamori M.
  • Journal Title: Biochimie. Volume: 113 Pages: 17-25
  • DOI: 10.1016/j.biochi.2015.01.013
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Absence of lactobacilli containing glycolipids with the α-galactose epitope and the enhanced fucosylation of a receptor glycolipid GA1 in the digestive tracts of immune-deficient scid mice. (2015)
  • Author(s): Iwamori M, Tanaka K, Adachi S, Aoki D, Nomura T
  • Journal Title: J Biochem Volume: Mar 9
  • NAID: 40020522527
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Potential impact of combined high- and low-risk human papillomavirus infection on the progression of cervical intraepithelial neoplasia 2 (2014)
  • Author(s): Okadome M, Saito T, Tanaka H, Nogawa T, Furuta R, Watanabe K, Kita T, Yamamoto K, Mikami M, Takizawa K
  • Journal Title: J Obstet Gynaecol Res Volume: 40 Issue: 2 Pages: 561-569
  • DOI: 10.1111/jog.12202
  • Peer Reviewed / Open Access
• [Journal Article] Predicting perioperative venous thromboembolism in Japanese gynecological patients (2014)
  • Author(s): Ikeda M, Kan-no H, Hayashi M, Tsukada H, Shida M, Hirasawa T, Muramatsu T,Ogushi Y,Mikami M
  • Journal Title: PLoS One Volume: 9(2)
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel glycobiomarker for ovarian cancer that detects clear cell carcinoma. (2014)
  • Author(s): Sogabe M, Nozaki H, Tanaka N, Kubota T, Kaji H, Kuno A, Togayachi A, Gotoh M, Nakanishi H, Nakanishi T, Mikami M, Suzuki N, Kiguchi K, Ikehara Y, Narimatsu H
  • Journal Title: J Proteome Res Volume: 7 Issue: 3 Pages: 1624-1635
  • DOI: 10.1021/pr401109n
  • Peer Reviewed / Open Access
• [Journal Article] Defect of tropomyosin-related kinase B isotype expression in ovarian clear cell adenocarcinoma (2014)
  • Author(s): Goto Y, Kametani Y*, Kikugawa A, Tsuda B, Miyazawa M, Kajiwara H, Terao Y, Takekoshi S, Nakamura N, Takeda S, Mikami M
  • Journal Title: BioScience Trends Volume: 8 Issue: 2 Pages: 93-100
  • DOI: 10.5582/bst.8.93
  • NAID: 130005054667
  • ISSN: 1881-7815, 1881-7823
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of lymphadenectomy for ovarian cancer (2014)
  • Author(s): Mikio Mikami
  • Journal Title: Journal of Gynecologic Oncology Volume: 25-4 Pages: 279-281
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Surgical Principles for Managing Stage IB2, IIA2, and IIB Uterine Cervical Cancer (Bulky Tumors) in Japan A Survey of the Japanese Gynecologic Oncology Group (2014)
  • Author(s): Mikio Mikami, Yoichi Aoki, Masaru Sakamoto, Muneaki Shimada, Nobuhiro Takeshima, Hisaya Fujiwara, Takashi Matsumoto, Tunekazu Kita, Ken Takizawa
  • Journal Title: International Journal of Gynecological Cancer Volume: 24 Issue: 7 Pages: 1333-1340
  • DOI: 10.1097/igc.0000000000000202
  • Peer Reviewed / Open Access
• [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
  • 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
  • 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
  • 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
• [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
• [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
  • 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
• [Presentation] Fully sialylated alpha-chain of complement 4-binding protein:Diagnostic utility for ovarian clear cell carcinoma (2016)
  • Author(s): M Mikami,K Tanabe,K Matsuo,M Miyazawa,M Hayashi,S Asai,M Ikeda,M Shida,T Hirasawa,R Sho
  • Organizer: SGO 47th Annual Meeting on Women's Cancer
  • Place of Presentation: San Diego Convention Center（アメリカ）
  • Year and Date: 2016-03-19
  • Int'l Joint Research
• [Presentation] ヒト胎盤における癌遺伝子TrkBと免疫抑制遺伝子PD-L1の共発現 (2015)
  • Author(s): 西上絵里奈、木南理仁、寺山隼人、坂部貢、石本人士、三上幹男、亀谷美恵
  • Organizer: 第30回日本生殖疫学会総会・学術集会
  • Place of Presentation: くまもと県民交流館パレア パレアホール（熊本県熊本市）
  • Year and Date: 2015-11-21
• [Presentation] 子宮頸癌ⅡB期の治療を考える-傍大動脈リンパ節郭清と基靱帯完全摘出について- (2015)
  • Author(s): 三上幹男
  • Organizer: 第53回日本癌治療学会学術集会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2015-10-29
• [Presentation] Surgery or CCRT for stage ⅡB cervical Cancer - Role of Radical Surgery - (2015)
  • Author(s): M Mikami,S Asai,M Ikwda,M Shida,T Hirasawa
  • Organizer: 19th INTERNATIONAL MEETING OF THE EUROPEAN SOCIETY OF GYNAECOLOGICAL ONCOLOGY (ESGO)
  • Place of Presentation: Acropolis Congress Center（フランス）
  • Year and Date: 2015-10-24
  • Int'l Joint Research
• [Presentation] 子宮頸癌ガイドライン-その検証・問題点・今後の登録事業への反映-子宮頸癌治療ガイドライン2007年版検証・問題点 (2015)
  • Author(s): 信田政子、池田仁惠、高橋史朗、小林広幸、永瀬智、三上幹男、八重樫伸生、片渕秀隆
  • Organizer: 第57回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: アイーナいわて県民情報交流センター（岩手県盛岡市）
  • Year and Date: 2015-08-07
• [Presentation] 卵巣明細胞腺癌に対する術後初回化学療法としてのパクリタキセル・カルボプラチン（TC）療法とイリノテカン・シスプラチン（CPT-P）療法のランダム化第Ⅲ相比較試験：GCIG/JGOG3017試験 (2015)
  • Author(s): 西野幸治、杉山徹、岡本愛光、榎本隆之、青木大輔、寺尾泰久、鈴木直、三上幹男、八重樫伸生、加藤聖子、吉川裕之、横山良仁、藤原恵一、落合和德
  • Organizer: 第67回日本産科婦人科学会学術講演会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-04-09
• [Presentation] 子宮頸がんに対する広汎子宮全摘術の合併症に関する全国調査 (2015)
  • Author(s): 喜多恒和、滝澤憲、藤原久也、山本嘉一郎、坂本優、青木陽一、島田宗昭、武隈宗孝、竹島信宏、西尾真、松元隆、三上幹男
  • Organizer: 第67回日本産科婦人科学会学術講演会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-04-09
• [Presentation] Surgical principles and status for managing stage IB2,ⅡA2,and ⅡB uterine cervical cancer (bulky tumors) in Japan (2014)
  • Author(s): Mikio Mikami
  • Organizer: The 20th Korean Gynecologic Oncology Group Symposium
  • Place of Presentation: Ajou University
  • Year and Date: 2014-10-25
  • Invited
• [Presentation] Role of lymphadenectomy for Ovarian Cancer (2014)
  • Author(s): Mikio Mikami
  • Organizer: The 20th Annual Symposium of Korean Society of Gynecologic Oncologists
  • Place of Presentation: Ajou University
  • Year and Date: 2014-10-24
  • Invited
• [Presentation] 免疫不全scidマウス消化管にはα-ガラクトースエピトープ含有糖脂質を持つ乳酸菌は棲息していない An absence of lactobacilli containing glycolipids with α-galactose epitope in the digestive tract of immune-deficient scid mice (2014)
  • Author(s): 岩森正男、岩森由里子、足立成基、野村大成、田中京子、青木大輔
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] ヒト子宮頸癌細胞におけるGM2糖鎖を持つガングリオシドの発現 Expression of gangliosides with GM2-carbohydrate determinant in human uterine cervical carcinoma-derived cells (2014)
  • Author(s): 田中京子、宮澤昌樹、三上幹男、青木大輔、木口一成、岩森正男
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Role of Sulfatide in adenocarcinoma of the cervix (2014)
  • Author(s): 宮澤昌樹、宮澤麻里子、杉山太朗、松井成明、藤井幸子、池田仁惠、信田政子、平澤猛、梶原博、村松俊成、岩森正男、三上幹男
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 乳酸菌の腸内共生と免疫の役割 (2014)
  • Author(s): 岩森正男、足立成基、野村大成, 田中京子、青木大輔
  • Organizer: 第56回日本脂質生化学会
  • Place of Presentation: 近畿大学東大阪
  • Year and Date: 2014-06-06 – 2014-06-07
• [Presentation] 各種乳酸菌の糖脂質の構造的特徴と抗原性 (2014)
  • Author(s): 南領将、谷河みなみ、枡田尚也、伊東玲芳、田中京子、青木大輔、岩森正男
  • Organizer: 第61回日本生化学会近畿支部例会
  • Place of Presentation: 京都産業大学
  • Year and Date: 2014-05-17
• [Presentation] Preoperative prediction of the para-aortic lymph node (PAN) metastasis in patients with cervical cancer (2014)
  • Author(s): M Hayashi,T Narayama,Y Hirano,Y Goto,M Ikeda,M Shida, Hirasawa,H Ishimoto,S Izumi,M Mikmi
  • Organizer: 第66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
  • Year and Date: 2014-04-18 – 2014-04-20