Analysis of fucosylated protein of high risk prostate cancer and the development of novel therapy

• Project/Area Number: 18K09132
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Kindai University (2020-2022); Osaka University (2018-2019)
• Principal Investigator: Fujita Kazutoshi 近畿大学, 医学部, 准教授 (50636181)
• Co-Investigator(Kenkyū-buntansha): 三善 英知 大阪大学, 大学院医学系研究科, 教授 (20322183) ; 野々村 祝夫 大阪大学, 大学院医学系研究科, 教授 (30263263)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2021: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 前立腺癌 / 糖鎖 / PSA / 糖鎖PSA / フコシル化 / バイオマーカー

Outline of Final Research Achievements

Fucosylation is one of the important glycosylation modifications in cancer and inflammation, and there are three types of fucosylation: Core, Lewis, and H-type. We developed a kit to measure core-type fucosylated PSA in blood using a microcapillary electrophoresis immunofluorescence assay, and found that core-type fucosylated PSA was significantly elevated in prostate cancer patients compared to prostate biopsy-negative patients. Core-type fucosylated PSA was also significantly elevated in prostate cancer patients with a Gleason score of 7 or higher, compared with Gleason score 6 and biopsy negative patients. Simultaneous measurement of S2,3 PSA with core-type fucosylated PSA further improved the accuracy of diagnosis of high-risk prostate cancer.

Academic Significance and Societal Importance of the Research Achievements

Core型フコシル化PSAが高リスク前立腺癌患者の血中で上昇しており、治療を行う必要のある前立腺癌患者を採血により診断できることが可能となった。また認可されたS2,3PSAと同時測定することによりその精度が更にあがることを明らかにした。測定方法は実臨床で使用されているュータスマイクロキャピラリー電気泳動免疫蛍光測定装置を用いており、実臨床で実施が可能で、短時間での測定が可能である。今後臨床性能試験を行い臨床応用を目指す。

Research Products

• [Journal Article] Establishment of a novel 70K Mac-2 binding protein antibody through screening of fucosylation-related antibodies (2023)
  • Author(s): Masuda Mika、Asuka Tatsuya、Terao Naoko、Nishino Shinsuke、Ikeda Shun、Takamatsu Shinji、Kondo Jumpei、Miyoshi Eiji
  • Journal Title: The Journal of Biochemistry Volume: - Issue: 6 Pages: 487-495
  • DOI: 10.1093/jb/mvad015
  • Peer Reviewed
• [Journal Article] Core Fucosylation Is Required for the Secretion of and the Enzymatic Activity of SOD3 in Nonsmall-Cell Lung Cancer Cells (2023)
  • Author(s): Ohkawa Yuki、Kitano Masato、Maeda Kento、Nakano Miyako、Kanto Noriko、Kizuka Yasuhiko、Seike Masahiro、Azuma Arata、Yamaguchi Yoshiki、Ookawara Tomomi、Miyoshi Eiji、Taniguchi Naoyuki
  • Journal Title: Antioxid Redox Signal. Volume: - Issue: 16-18 Pages: 227-234
  • DOI: 10.1089/ars.2022.0010
  • Peer Reviewed / Open Access
• [Journal Article] Lewis glycosphingolipids as critical determinants of TRAIL sensitivity in cancer cells (2022)
  • Author(s): Fukuoka Tomoya、Moriwaki Kenta、Takamatsu Shinji、Kondo Jumpei、Tanaka-Okamoto Miki、Tomioka Azusa、Semba Manami、Komazawa-Sakon Sachiko、Kamada Yoshihiro、Kaji Hiroyuki、Miyamoto Yasuhide、Inoue Masahiro、Bessho Kazuhiko、Miyoshi Yoko、Ozono Keiichi、Nakano Hiroyasu、Miyoshi Eiji
  • Journal Title: Oncogene Volume: 41 Issue: 38 Pages: 4385-4396
  • DOI: 10.1038/s41388-022-02434-3
  • Peer Reviewed
• [Journal Article] Simultaneous analysis of serum α2,3-linked sialylation and core-type fucosylation of prostate-specific antigen for the detection of high-grade prostate cancer (2021)
  • Author(s): Hatano Koji、Yoneyama Tohru、Hatakeyama Shingo、Tomiyama Eisuke、Tsuchiya Mutsumi、Nishimoto Mitsuhisa、Yoshimura Kazuhiro、Miyoshi Eiji、Uemura Hirotsugu、Ohyama Chikara、Nonomura Norio、Fujita Kazutoshi
  • Journal Title: British Journal of Cancer Volume: 126 Issue: 5 Pages: 764-770
  • DOI: 10.1038/s41416-021-01637-x
  • Peer Reviewed / Open Access
• [Journal Article] Fucosylation in Urological Cancers (2021)
  • Author(s): Fujita Kazutoshi、Hatano Koji、Hashimoto Mamoru、Tomiyama Eisuke、Miyoshi Eiji、Nonomura Norio、Uemura Hirotsugu
  • Journal Title: International Journal of Molecular Sciences Volume: 22 Issue: 24 Pages: 13333-13333
  • DOI: 10.3390/ijms222413333
  • Peer Reviewed / Open Access
• [Journal Article] Serum core-type fucosylated prostate-specific antigen index for the detection of high-risk prostate cancer. (2021)
  • Author(s): Fujita K, Hatano K, Tomiyama E, Hayashi Y, Matsushita M, Tsuchiya M, Yoshikawa T, Date M, Miyoshi E, Nonomura N.
  • Journal Title: Int J Cancer. Volume: Epub ahead of print Issue: 12 Pages: 1-8
  • DOI: 10.1002/ijc.33517
  • Peer Reviewed / Open Access
• [Journal Article] Detection of fucosylated haptoglobin using the 10-7G antibody as a biomarker for evaluating endoscopic remission in ulcerative colitis (2021)
  • Author(s): Motooka Kei、Morishita Koichi、Ito Nami、Shinzaki Shinichiro、Tashiro Taku、Nojima Satoshi、Shimizu Kayoko、Date Mutsuhiro、Sakata Natsumi、Yamada Momoko、Takamatsu Shinji、Kamada Yoshihiro、Iijima Hideki、Mizushima Tsunekazu、Morii Eiichi、Takehara Tetsuo、Miyoshi Eiji
  • Journal Title: World Journal of Gastroenterology Volume: 27 Issue: 2 Pages: 162-175
  • DOI: 10.3748/wjg.v27.i2.162
  • Peer Reviewed / Open Access
• [Journal Article] Loss of core fucosylation reduces low-density lipoprotein receptor expression in hepatocytes by inducing PCSK9 production (2020)
  • Author(s): Kamada Yoshihiro、Yamamoto Akiko、Fujiyoshi Anna、Koseki Masahiro、Morishita Koichi、Asuka Tatsuya、Takamatsu Shinji、Sakata Yasushi、Takehara Tetsuo、Taniguchi Naoyuki、Miyoshi Eiji
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 527 Issue: 3 Pages: 682-688
  • DOI: 10.1016/j.bbrc.2020.05.019
  • Peer Reviewed / Open Access
• [Journal Article] Identification of the epitope of 10-7G glycan antibody to recognize cancer-associated haptoglobin (2020)
  • Author(s): Morishita Koichi、Maki Yuta、Takamatsu Shinji、Ito Nami、Koda Sayaka、Motooka Kei、Kamada Yoshihiro、Kajihara Yasuhiro、Miyoshi Eiji
  • Journal Title: Analytical Biochemistry Volume: 593 Pages: 113588-113588
  • DOI: 10.1016/j.ab.2020.113588
  • Peer Reviewed
• [Journal Article] Establishment and characterization of a fucosylated α-fetoprotein-specific monoclonal antibody: a potential application for clinical research (2019)
  • Author(s): Egashira Yuriko、Suganuma Masatoshi、Kataoka Yukiko、Higa Yukiko、Ide Nobuyuki、Morishita Koichi、Kamada Yoshihiro、Gu Jianguo、Fukagawa Koji、Miyoshi Eiji
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 12359-12370
  • DOI: 10.1038/s41598-019-48821-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Urinary biomarkers of prostate cancer (2018)
  • Author(s): Fujita Kazutoshi、Nonomura Norio
  • Journal Title: International Journal of Urology Volume: 25 Issue: 9 Pages: 770-779
  • DOI: 10.1111/iju.13734
  • Peer Reviewed / Open Access
• [Presentation] Simultaneous analysis of serum a 2,3-linked sialylation and core-type fucosylation of PSA for the detection of clinically significant prostate cancer (2021)
  • Author(s): 波多野 浩士, 米山 徹, 畠山 真吾, 藤田 和利, 三善 英知, 吉村 一宏, 植村 天受, 大山 力, 野々村 祝夫
  • Organizer: 日本泌尿器科学会総会 109回
• [Presentation] 藤田 和利 (2021)
  • Author(s): S2,3PSAとFucPSA同時測定による高Gleason score前立腺癌診断
  • Organizer: 日本泌尿器腫瘍学会第7回学術集会
• [Presentation] 自動化マイクロキャピラリー電気泳動法による高Gleason前立腺癌診断法のための血中Core型フコシル化PSA測定法の開発 (2020)
  • Author(s): 藤田 和利, 林 裕次郎, 吉川 友康, 山下 謙一郎, 冨山 栄輔, 松下 慎, 中野 剛佑, 加藤 大悟, 波多野 浩士, 河嶋 厚成, 氏家 剛, 植村 元秀, 吉村 一宏, 植村 天受, 三善 英知, 野々村 祝夫
  • Organizer: 第79回日本癌学会学術総会
• [Presentation] マイクロキャピラリー電気泳動免疫蛍光測定装置によるcore型フコシル化PSA測定法の開発 (2020)
  • Author(s): 藤田和利、吉川友康、山下謙一郎 冨山栄輔、松下慎、林裕次郎、 加藤大悟、波多野浩士、河嶋厚成、氏家剛、植村元秀、三善英知、野々村祝夫
  • Organizer: 第108回日本泌尿器科学会総会
• [Presentation] 前立腺癌におけるフコシル化とバイオマーカーへの応用 (2019)
  • Author(s): 藤田和利
  • Organizer: 第39回日本分子腫瘍マーカー研究会
  • Invited
• [Remarks] 悪性度の高い前立腺がんを診断する新たな高感度測定法を確立
  • URL: https://resou.osaka-u.ac.jp/ja/research/2021/20210219_2
• [Remarks] 悪性度の高い前立腺がんを診断する新たな高感度測定法を確立
  • URL: https://newscast.jp/news/0271941
• [Patent(Industrial Property Rights)] 血中フコシル化PSAによるハイリスク前立腺癌診断バイオマーカーの開発 (2020)
  • Inventor(s): 藤田和利、三善英知、野々村祝夫、吉川友康、伊達睦廣
  • Industrial Property Rights Holder: 藤田和利、三善英知、野々村祝夫、吉川友康、伊達睦廣
  • Industrial Property Rights Type: 特許
  • Filing Date: 2020