Development of histological diagnosis method and predictive diagnosis method for ovarian cancer using liquid biopsy before the surgery

• Project/Area Number: 18K09308
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Kyoto University
• Principal Investigator: Yamaguchi Ken 京都大学, 医学研究科, 講師 (20378772)
• Co-Investigator(Kenkyū-buntansha): 馬場 長 岩手医科大学, 医学部, 教授 (60508240) ; 万代 昌紀 京都大学, 医学研究科, 教授 (80283597)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 婦人科がん / リキッドバイオプシー / DNAメチル化 / SNV / 卵巣明細胞癌 / 卵巣癌 / cell free DNA / 一塩基変異

Outline of Final Research Achievements

Comprehensive DNA methylation analysis using ovarian cancer tissues revealed that 22 genes were activated and 276 genes were suppressed that were considered to be functionally important in clear cell cancer and were regulated by DNA methylation. Exome sequence analysis using clear cell ovarian cancer revealed that there are many SNVs and copy count abnormalities in the genes involved in KRAS-PI3K signal, MYC-RB signal, and SWI / SNF complex in ovarian clear cell carcinoma. The concentration of cell-free DNA was measured from the blood of patients with ovarian cancer, endometriosis, and healthy counterparts, The concentrations of cell-free DNA increased was highest in advanced ovarian cancer, and lowest in healthy counterparts.

Academic Significance and Societal Importance of the Research Achievements

卵巣明細胞癌に特徴的なDNAメチル化やコピー数異常、SNVを明らかにした。これはリキッドバイオプシーの検査対象になり得ると考える。健常人、子宮内膜症、卵巣癌患者のcell-free DNAの濃度を測定し、実現性を検証した。

Research Products

• [Journal Article] Serum lactate dehydrogenase is a possible predictor of platinum resistance in ovarian cancer (2020)
  • Author(s): Ikeda Asami、Yamaguchi Ken、Yamakage Hajime、Abiko Kaoru、Satoh-Asahara Noriko、Takakura Kenji、Konishi Ikuo
  • Journal Title: Obstetrics & Gynecology Science Volume: 63 Issue: 6 Pages: 709-718
  • DOI: 10.5468/ogs.20117
  • Peer Reviewed
• [Journal Article] Anti-VEGF therapy resistance in ovarian cancer is caused by GM-CSF-induced myeloid-derived suppressor cell recruitment. (2020)
  • Author(s): Horikawa N, Abiko K, Matsumura N, Baba T, Hamanishi J, Yamaguchi K, Murakami R, Taki M, Ukita M, Hosoe Y, Koshiyama M, Konishi I, Mandai M.
  • Journal Title: Br J Cancer. Volume: 122(1) Issue: 6 Pages: 778-788
  • DOI: 10.1038/s41416-019-0725-x
  • Peer Reviewed / Open Access
• [Journal Article] VISTA expressed in tumour cells regulates T cell function (2018)
  • Author(s): Mulati Kumuluzi、Hamanishi Junzo、Matsumura Noriomi、Chamoto Kenji、Mise Nathan、Abiko Kaoru、Baba Tsukasa、Yamaguchi Ken、Horikawa Naoki、Murakami Ryusuke、Taki Mana、Budiman Kharma、Zeng Xiang、Hosoe Yuko、Azuma Miyuki、Konishi Ikuo、Mandai Masaki
  • Journal Title: British Journal of Cancer Volume: 120 Issue: 1 Pages: 115-127
  • DOI: 10.1038/s41416-018-0313-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Antitumor Effect of Nivolumab on Subsequent Chemotherapy for Platinum‐Resistant Ovarian Cancer (2018)
  • Author(s): Inayama Yoshihide、Hamanishi Junzo、Matsumura Noriomi、Murakami Ryusuke、Abiko Kaoru、Yamaguchi Ken、Baba Tsukasa、Horie Katsuyuki、Konishi Ikuo、Mandai Masaki
  • Journal Title: The Oncologist Volume: 23 Issue: 11 Pages: 1382-1384
  • DOI: 10.1634/theoncologist.2018-0167
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Mucinous adenocarcinoma, gastric type of the uterine cervix: clinical features and HER2 amplification (2018)
  • Author(s): Nakamura Ayano、Yamaguchi Ken、Minamiguchi Sachiko、Murakami Ryusuke、Abiko Kaoru、Hamanishi Junzo、Kondoh Eiji、Baba Tsukasa、Mandai Masaki、Matsumura Noriomi
  • Journal Title: Medical Molecular Morphology Volume: 52 Issue: 1 Pages: 52-59
  • DOI: 10.1007/s00795-018-0202-2
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The effect of the type of dietary protein on the development of ovarian cancer (2018)
  • Author(s): Taha Ahmed A.A.、Koshiyama Masafumi、Matsumura Noriomi、Abiko Kaoru、Yamaguchi Ken、Hamanishi Jyunzo、Baba Tsukasa、Kharma Budiman、Mohamed Ibrahim Hassanin、Ameen Magdy Mohamed、Ismail Salah Ali、Konishi Ikuo、Mandai Masaki
  • Journal Title: Oncotarget Volume: 9 Issue: 35 Pages: 23987-23999
  • DOI: 10.18632/oncotarget.25253
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Snail promotes ovarian cancer progression by recruiting myeloid-derived suppressor cells via CXCR2 ligand upregulation. (2018)
  • Author(s): Taki M, Abiko K, Baba T, Hamanishi J, Yamaguchi K, Murakami R, Yamanoi K, Horikawa N, Hosoe Y, Nakamura E, Sugiyama A, Mandai M, Konishi I, Matsumura N.
  • Journal Title: Nature communications Volume: Apr 27;9(1) Issue: 1 Pages: 1685-1685
  • DOI: 10.1038/s41467-018-03966-7
  • NAID: 120006462510
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Comprehensive RNA-seq Analysis Identifies the Progression Signature in Ovarian Clear Cell Carcinoma (2019)
  • Author(s): Shiro Takamatsu, Noriomi Matsumura*, Ryusuke Murakami, Ken Yamaguchi, Junzo Hamanishi, J.B.Brown**, Masaki Mandai
  • Organizer: 第71回日本産科婦人科学会学術講演会
• [Presentation] Genomic alterations induces metabolic change through the activation of PDK2 in ovarian clear cell carcinoma. (2018)
  • Author(s): Sachiko Kitamura, Ken Yamaguchi, Ryusuke Murakami, Kaoru Abiko, Junzo Hamanishi, Tsukasa Baba, Noriomi Matsumura, Masaki Mandai
  • Organizer: 第70回日本産科婦人科学会学術講演会
• [Presentation] PDK2 inhibition has synergic effect with cisplatin targeting mitochondrial metabolism in ovarian clear cell carcinoma. (2018)
  • Author(s): Sachiko Kitamura, Ken Yamaguchi, Ryusuke Murakami, Kaoru Abiko, Junzo Hamanishi, Tsukasa Baba, Masaki Mandai
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] PDK inhibition has synergic effect with cisplatin targeting mitochondrial metabolism in ovarian clear cell carcinoma. (2018)
  • Author(s): Sachiko Kitamura, Ken Yamaguchi, Ryusuke Murakami, Kaoru Abiko, Junzo Hamanishi, Tsukasa Baba, Noriomi Matsumura, Masaki Mandai
  • Organizer: The 17th Biennial Meeting of the International Gynecologic Cancer Society
  • Int'l Joint Research
• [Presentation] Clinicopathological Feature and HER-2 Amplification in Gastric Type Adenocarcinoma of the Uterine Cervix. (2018)
  • Author(s): Ayano Nakamura, Ken Yamaguchi, Tsukasa Baba, Noriomi Matsumura, and Masaki Mandai
  • Organizer: American College of Obstetricians and Gynecologists
  • Int'l Joint Research
• [Presentation] VISTA expressed in tumor cells regulates T cell function VISTA expressed in tumor cells regulates T cell function (2018)
  • Author(s): Murat Kumuruz, 濵西 潤三, 松村 謙臣, 茶本 健司, 三瀬 名丹, 安彦 郁, 馬場 長, 山口 建, 村上 隆介, 細江 裕子, 東 みゆき, 小西 郁夫, 万代 昌紀
  • Organizer: 日本癌学会学術総会
• [Presentation] 卵巣明細胞癌においてミトコンドリア代謝を標的とするPDK2阻害はシスプラチンと合成致死性を示す (2018)
  • Author(s): 北村幸子、山口 建、村上隆介、安彦 郁、濵西潤三、馬場 長、万代昌紀
  • Organizer: 第6回婦人科がんバイオマーカー研究会