既成概念を打破する血清網羅的糖ペプチド解析による卵巣癌早期診断の社会実装

2020 Fiscal Year Annual Research Report

• Project/Area Number: 20H03828
• Research Institution: Tokai University
• Principal Investigator: 三上 幹男 東海大学, 医学部, 教授 (30190606)
• Co-Investigator(Kenkyū-buntansha): 信田 政子 東海大学, 医学部, 講師 (10338717) ; 池田 仁惠 東海大学, 医学部, 講師 (20365993) ; 町田 弘子 東海大学, 医学部, 助教 (40803507) ; 佐藤 健二 東海大学, 医学部, 講師 (50306825) ; 平澤 猛 東海大学, 医学部, 准教授 (70307289) ; 今西 規 東海大学, 医学部, 教授 (80270461) ; 林 優 東海大学, 医学部, 助教 (80631837)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 卵巣癌 / 子宮内膜症 / 血清腫瘍マーカー / 糖ペプチド / CSGSA / 深層学習 / OPLS-DA

Outline of Annual Research Achievements

FS-C4BP (Fully-sialylated alpha-chain of complement 4-binding protein)の簡易測定系作成に関しては、レクチン電気泳動とウェスタンブロットによってFS-C4BPの分子構造から予想されるように原理通り健常人血清と卵巣癌患者血清の選別、個々の例での測定は可能であった。
網羅的血清糖ペプチドスペクトラ解析 (CSGSA: Comprehensive Serum Glycopeptide Spectra Analysis)により得た糖ペプチドピークを2次元バーコード化(画像化)し人工知能（深層学習）によって学習させることで、健常人、良性疾患、卵巣癌を選別することが可能であった(Tanabe K, Mikami M, et al. Comprehensive Serum Glycopeptide Spectra Analysis Combined with Artificial Intelligence (CSGSA-AI) to Diagnose Early-Stage Ovarian Cancer. Cancers (Basel). 2020 Aug 21;12(9):E2373. doi: 10.3390/cancers12092373.)。また同様にCSGSAにより得た糖ペプチドピークを用いて統計学的解析（OPLS-DA）によって同様に選別することが可能であった（Matsuo K, Mikami M, et al, Utility of Comprehensive Serum Glycopeptide Spectra Analysis (CSGSA) for the Detection of Early Stage Epithelial Ovarian Cancer. Cancers (Basel). 2020 Aug 21;12(9):E2374. doi: 10.3390/cancers12092374.）。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

FS-C4BP (Fully-sialylated alpha-chain of complement 4-binding protein)の簡易測定系作成に関しては、原理的に分離が成功した。
CSGSAにより得た糖ペプチドピークの深層学習による分析、OPLS-DAによる分析によって卵巣癌例の選別の可能性が示唆された。

Strategy for Future Research Activity

本研究では多数例の血清の収集が重要であるが、2021年3月末現在、卵巣癌、婦人科良性腫瘍例、健常人例の合計で2082例を収集し終えており、FS-C4BP測定系作成に関してはより簡易キット化に向けての方法の開発を行う。またCSGSAによる糖ペプチドデータの測定を順次行い、深層学習による分析、OPLS-DAによる分析を続行していく。また将来を見据えて社会実装実現のために臨床試験についての詳細な検討・立案を開始する予定である。

Research Products

• [Journal Article] A randomized phase III trial of adjuvant chemotherapy versus concurrent chemoradiotherapy for postoperative cervical cancer: Japanese Gynecologic Oncology Group study (JGOG1082) (2021)
  • Author(s): Furusawa A, Takekuma M, Mori K, Usami T, Kondo E, Nishio S, Nishino K, Miyamoto Y, Yoshimura R, Watanabe M, Mikami M, Enomoto T
  • Journal Title: Int J Gynecol Cancer Volume: 31(4) Pages: 623-626
  • DOI: 10.1136/ijgc-2020-002344
  • Peer Reviewed / Open Access
• [Journal Article] The 2020 Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer (2021)
  • Author(s): Tokunaga H, Mikami M, Nagase S, Kobayashi Y, Tabata T, Kaneuchi M, Satoh T, Hirashima Y, Matsumura N, Yokoyama Y, Kawana K, Kyo S, Aoki D, Katabuchi H.
  • Journal Title: J Gynecol Oncol Volume: 32(2) Pages: e49
  • DOI: 10.3802/jgo.2021.32.e49.
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive Serum Glycopeptide Spectra Analysis Combined with Artificial Intelligence (CSGSA-AI) to Diagnose Early-Stage Ovarian Cancer. (2020)
  • Author(s): Tanabe K, Ikeda M, Hayashi M, Matsuo K, Yasaka M, Machida H, Shida M, Katahira T, Imanishi T, Hirasawa T, Sato K, Yoshida H, Mikami M.
  • Journal Title: Cancers (Basel) Volume: 12（9） Pages: E2373
  • DOI: 10.3390/cancers12092373
  • Peer Reviewed / Open Access
• [Journal Article] Lymphadenectomy for primary ovarian cancer: a systematic review and meta-analysis. (2020)
  • Author(s): Chiyoda T, Sakurai M, Satoh T, Nagase S, Mikami M, Katabuchi H, Aoki D.
  • Journal Title: J Gynecol Oncol Volume: 31(5) Pages: e67
  • DOI: 10.3802/jgo.2020.31.e67.
  • Peer Reviewed / Open Access
• [Journal Article] Epidemiological guideline influence on the therapeutic trend and patient outcome of uterine cervical cancer in Japan: Japan society of gynecologic oncology guideline evaluation committee project. (2020)
  • Author(s): Shigeta S, Shida M, Nagase S, Ikeda M, Takahashi F, Shibata T, Yamagami W, Katabuchi H, Yaegashi N, Aoki D, Mikami M
  • Journal Title: Gynecol Oncol Volume: 159 Pages: 248-255
  • DOI: 10.1016/j.ygyno.2020.07.023.
  • Peer Reviewed / Open Access
• [Journal Article] Utility of Comprehensive Serum Glycopeptide Spectra Analysis (CSGSA) for the Detection of Early Stage Epithelial Ovarian Cancer. (2020)
  • Author(s): Matsuo K, Tanabe K, Hayashi M, Ikeda M, Yasaka M, Machida H, Shida M, Sato K, Yoshida H, Hirasawa T, Imanishi T, Mikami M.
  • Journal Title: Cancers (Basel) Volume: 12(9) Pages: E2374
  • DOI: 10.3390/cancers12092374.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fertility-sparing trachelectomy for early-stage cervical cancer: A proposal of an ideal candidate. (2020)
  • Author(s): Machida H, Iwata T, Okugawa K, Matsuo K, Saito T, Tanaka K, Morishige K, Kobayashi H, Yoshino K, Tokunaga H, Ikeda T, Shozu M, Yaegashi N, Enomoto T, Mikami M.
  • Journal Title: Gynecol Oncol Volume: 156(2) Pages: 341-348
  • DOI: 10.1016/j.ygyno.2019.11.021
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Japan Society of Gynecologic Oncology 2018 guidelines for treatment of uterine body neoplasms. (2020)
  • Author(s): Yamagami W, Mikami M, Nagase S, Tabata T, Kobayashi Y, Kaneuchi M, Kobayashi H, Yamada H, Hasegawa K, Fujiwara H, Katabuchi H, Aoki D.
  • Journal Title: J Gynecol Oncol Volume: 31(1) Pages: e18
  • DOI: 10.3802/jgo.2020.31.e18.
  • Peer Reviewed / Open Access
• [Journal Article] A retrospective study for investigating the relationship between old and new staging systems with prognosis in ovarian cancer using gynecologic cancer registry of Japan Society of Obstetrics and Gynecology (JSOG): disparity between serous carcinoma and clear cell carcinoma. (2020)
  • Author(s): Yamagami W, Nagase S, Takahashi F, Ino K, Hachisuga T, Mikami M, Enomoto T, Katabuchi H, Aoki D.
  • Journal Title: J Gynecol Oncol Volume: 31(3) Pages: e45
  • DOI: 10.3802/jgo.2020.31.e45.
  • Peer Reviewed / Open Access
• [Journal Article] Management of Stage IIB Cervical Cancer: an Overview of the Current Evidence. (2020)
  • Author(s): Matsuzaki S, Klar M, Mikami M, Shimada M, Grubbs BH, Fujiwara K, Roman LD, Matsuo K.
  • Journal Title: Curr Oncol Rep Volume: 22(3) Pages: 22-28
  • DOI: 10.1007/s11912-020-0888-x.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Survival Outcome and Perioperative Complication Related to Neoadjuvant Chemotherapy With Carboplatin and Paclitaxel for Advanced Ovarian Cancer: A Systematic Review and Meta-Analysis. (2020)
  • Author(s): Machida H, Tokunaga H, Matsuo K, Matsumura N, Kobayashi Y, Tabata T, Kaneuchi M, Nagase S, Mikami M.
  • Journal Title: Eur J Surg Oncol Volume: 46(5) Pages: 868-875
  • DOI: 10.1016/j.ejso.2019.11.520
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Proposal of a Two-Tier System in Grouping Adenocarcinoma of the Uterine Cervix. (2020)
  • Author(s): Machida H, Matsuo K, Matsuzaki S, Yamagami W, Ebina Y, Kobayashi Y, Tabata T, Kaneuchi M, Nagase S, Enomoto T, Mikami M.
  • Journal Title: Cancers (Basel) Volume: 12(5) Pages: E1251
  • DOI: 10.3390/cancers12051251.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human PZP and common marmoset A2ML1 as pregnancy related proteins. (2020)
  • Author(s): Kashiwagi H, Ishimoto H, Izumi SI, Seki T, Kinami R, Otomo A, Takahashi K, Kametani F, Hirayama N, Sasaki E, Shiina T, Sakabe K, Mikami M, Kametani Y.
  • Journal Title: Sci Rep Volume: 10(1) Pages: 5088
  • DOI: 10.1038/s41598-020-61714-8
  • Peer Reviewed / Open Access
• [Journal Article] Investigation of clinicopathological features of vulvar cancer in 1068 patients: A Japanese Gynecologic Oncology Group (JGOG) nationwide survey study. (2020)
  • Author(s): Nishio S, Murotani K, Nakao S, Takenaka M, Suzuki S, Aoki Y, Todo Y, Hosaka M, Nakai H, Katabuchi H, Nishi H, Takekuma M, Mikami M, Enomoto T.
  • Journal Title: Gynecol Oncol Volume: 159 Pages: 449-455
  • DOI: 10.1016/j.ygyno.2020.08.019
  • Peer Reviewed / Open Access
• [Journal Article] Utility of the 3-tier grouping system for survival discriminatory ability in stage IIA cervical cancer. (2020)
  • Author(s): Matsuo K, Nusbaum DJ, Klar M, Matsuzaki S, Grubbs BH, Machida H, Konishi I, Mikami M, Roman LD.
  • Journal Title: Eur J Surg Oncol Volume: 47(2) Pages: 331-337
  • DOI: 10.1016/j.ejso.2020.06.014
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prevention and practice during the COVID-19 emergency declaration period in Japanese obstetrical/gynecological facilities. (2020)
  • Author(s): Komatsu H, Banno K, Yanaihara N, and Tadashi Kimura, Board Members of Japan Society of Obatetrics and Gynecology(Aoki D.Mikami M et al)
  • Journal Title: J Obstet Gynaecol Res Volume: 46(11) Pages: 2237-2241
  • DOI: 10.1111/jog.14432
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of pathological and clinical characteristics of cervical conization according to age group in Japan. (2020)
  • Author(s): Murakami I, Ohno A, Ikeda M, Yamashita H, Mikami M, Kobayashi Y, Nagase S, Yokoyama M, Enomoto T, Katabuchi H.
  • Journal Title: Heliyon Volume: 6(10) Pages: e05193
  • DOI: 10.1016/j.heliyon.2020.e05193
  • Peer Reviewed / Open Access
• [Journal Article] Impact of lymphadenectomy on the treatment of endometrial cancer using data from the JSOG cancer registry (2020)
  • Author(s): Saotome K, Yamagami W, Machida H, Ebina Y, Kobayashi Y, Tabata T, Kaneuchi M, Nagase S, Enomoto T, Aoki D, Mikami M.
  • Journal Title: Obstet Gynecol Sci Volume: 64(1) Pages: 80-89
  • DOI: 10.5468/ogs.20186
  • Peer Reviewed / Open Access
• [Journal Article] Usefulness of laparoscopic restaging surgery for patients diagnosed with apparent early ovarian/fallopian tubal cancer by a prior surgery, a case control observational study in a single institute in Japan. (2020)
  • Author(s): Yoshida H, Yamamoto M, Shigeta H, Yasaka M, Machida H, Ikeda M, Shida M, Hirasawa T, Mikami M.
  • Journal Title: Eur J Gynaecol Oncol Volume: 41(6) Pages: 960-968
  • DOI: 10.31083/j.ejgo.2020.06.2224
  • Peer Reviewed / Open Access
• [Journal Article] Surgical margin status and recurrence pattern in invasive vulvar Paget's disease: A Japanese Gynecologic Oncology Group study. (2020)
  • Author(s): Matsuo K, Nishio S, Matsuzaki S, Iwase H, Kagami S, Soeda S, Usui H, Nishikawa R, Mikami M, Enomoto T.
  • Journal Title: Gynecol Oncol Volume: 160(3) Pages: 748-754
  • DOI: 10.1016/j.ygyno.2020.12.023
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hypoxia-inducible Factor-1α Suppression in Ovarian Clear-cell Carcinoma Cells by Silibinin Administration. (2020)
  • Author(s): Mariko Miyazawa, M Yasuda, Masaki Miyazawa, N Ogane, T Katoh, M Yano, T Hirasawa, M Mikami and H Ishimoto.
  • Journal Title: Anticancer Research Volume: 40(12) Pages: 6791-6798
  • DOI: 10.21873/anticanres.14702
  • Peer Reviewed / Open Access
• [Presentation] NGS-based molecular profiling ( a multi-center collaborative, observation study in Japan) highlights pathogenic variants of DNA-repair genes in advanced or recurrent endometrial cancer. (2020)
  • Author(s): Fujiwara H, Oda K, Takahashi N, Sakata J, Taneichi A, Ikeda M, Tanikawa M, Kusakabe M, Mitsuhashi A, Kobayashi Y, Yamashita H, Suzuki N, Akiyama A, Tokunaga H, Tanaka N, Mikami M
  • Organizer: ASCO 2020 The American Society of Clinical Oncology
  • Int'l Joint Research