Elucidation of the pathogenesis of ovarian endometrioid carcinoma using single cell sequencing

• Project/Area Number: 20K09638
• 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: Niigata University
• Principal Investigator: Adachi Sosuke 新潟大学, 医歯学総合研究科, 特任准教授 (50613147)
• Co-Investigator(Kenkyū-buntansha): 吉原 弘祐 新潟大学, 医歯学系, 教授 (40547535) ; 田村 亮 新潟大学, 医歯学総合病院, 助教 (70650620)
• Project Period (FY): 2020-04-01 – 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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 卵巣類内膜癌 / 単一細胞シークエンス / 子宮内膜症 / 子宮内膜 / 卵巣癌

Outline of Research at the Start

子宮内膜症から卵巣類内膜癌への移行部位に注目して、単一細胞シークエンスを行うことで、内膜症から癌に移行するにつれて蓄積されるゲノム・エピゲノム異常を細胞レベルで明らかにし、卵巣類内膜癌の発症メカニズムを解明する。

Outline of Final Research Achievements

To investigate the progression from endometrium to endometrioid carcinoma via endometriosis, we focused on cancer-related gene mutations in normal endometrium. 32 women were sampled, 891 gland ducts were isolated, and single gland duct sequencing was performed. The most frequently mutated genes in normal endometrium were PIK3CA and KRAS, which were mutated in 15.6% and 10.9% of all cases, respectively. The median of mutation allele frequency of each endometrial gland was around 0.5, and almost all glands were monoclonal. Whole genome sequencing of single endometrial gland was also performed after recording the location of endometrial glands collected from the endometrium tissue and revealed that normal endometrial glands with cancer-associated gene mutations were spatially spread out in the endometrium tissue.

Academic Significance and Societal Importance of the Research Achievements

今回の対象疾患は女性の命に関わる疾患であるが、治療が奏効してもQOLを低下させてしまうため、予防が重要になる。本研究成果は、子宮内膜症や卵巣類内膜癌の発症予防に貢献でき、女性のQOL向上につながるポテンシャルのある研究である。

Research Products

• [Journal Article] Challenges for clinical application of “TRACEBACK” study: testing of historical Tubo-Ovarian cancer patients for hereditary risk genes (2023)
  • Author(s): Sekine Masayuki、Isobe Masanori、Nishino Koji、Adachi Sosuke、Suda Kazuaki、Yoshihara Kosuke
  • Journal Title: Annals of Translational Medicine Volume: 11 Issue: 8 Pages: 295-295
  • DOI: 10.21037/atm-23-352
  • Peer Reviewed / Open Access
• [Journal Article] The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions (2023)
  • Author(s): Rahmioglu Nilufer, ..., Sosuke Adachi, et al.
  • Journal Title: Nature Genetics Volume: 55 Issue: 3 Pages: 423-436
  • DOI: 10.1038/s41588-023-01323-z
  • Peer Reviewed / Open Access
• [Journal Article] Problems with catch-up HPV vaccination after resumption of proactive recommendations (2022)
  • Author(s): Sekine Masayuki、Yamaguchi Manako、Kudo Risa、Hanley Sharon J B、Ueda Yutaka、Kurosawa Megumi、Adachi Sosuke、Miyagi Etsuko、Hara Megumi、Enomoto Takayuki
  • Journal Title: The Lancet Oncology Volume: 23 Issue: 8 Pages: 972-973
  • DOI: 10.1016/s1470-2045(22)00259-5
  • Peer Reviewed
• [Journal Article] Effectiveness of human papillomavirus vaccine against cervical precancer in Japan: Multivariate analyses adjusted for sexual activity (2022)
  • Author(s): Kudo Risa、Sekine Masayuki、Yamaguchi Manako、Hara Megumi、Hanley Sharon J. B.、Kurosawa Megumi、Adachi Sosuke、Ueda Yutaka、Miyagi Etsuko、Ikeda Sayaka、Yagi Asami、Enomoto Takayuki
  • Journal Title: Cancer Science Volume: 113 Issue: 9 Pages: 3211-3220
  • DOI: 10.1111/cas.15471
  • Peer Reviewed / Open Access
• [Journal Article] Long-Term Effects of Human Papillomavirus Vaccination in Clinical Trials and Real-World Data: A Systematic Review (2022)
  • Author(s): Kurosawa M, Sekine M *, Yamaguchi M, Kudo R, Hanley SJB, Hara M, Adachi S, Ueda Y, Miyagi E, Ikeda S, Yagi A, Enomoto T.
  • Journal Title: Vaccines Volume: Feb 8;10(2) Issue: 2 Pages: 256-256
  • DOI: 10.3390/vaccines10020256
  • Peer Reviewed / Open Access
• [Journal Article] Long-term effectiveness of HPV vaccination against HPV infection in young Japanese women: Real-world data (2022)
  • Author(s): Kurosawa M, Sekine M *, Yamaguchi M, Kudo R, Hanley SJB, Hara M, Adachi S, Ueda Y, Miyagi E, Ikeda S, Yagi A, Enomoto T.
  • Journal Title: Cancer Sci. Volume: 113(4) Issue: 4 Pages: 1435-1440
  • DOI: 10.1111/cas.15282
  • Peer Reviewed
• [Journal Article] Suspension of proactive recommendations for HPV vaccination has led to a significant increase in HPV infection rates in young Japanese women: real-world data (2021)
  • Author(s): Sekine M, Yamaguchi M, Kudo R, Hanley SJB, Ueda Y, Adachi S, Kurosawa M, Miyagi E, Hara M, Enomoto T.
  • Journal Title: Lancet Reg Health West Pac. Volume: Oct 21;16 Pages: 100300-100300
  • DOI: 10.1016/j.lanwpc.2021.100300
  • Peer Reviewed
• [Journal Article] Cervical Cancer Protection in Japan: Where Are We? (2021)
  • Author(s): Yagi Asami、Ueda Yutaka、Kakuda Mamoru、Nakagawa Satoshi、Hiramatsu Kosuke、Miyoshi Ai、Kobayashi Eiji、Kimura Toshihiro、Kurosawa Megumi、Yamaguchi Manako、Adachi Sosuke、Kudo Risa、Sekine Masayuki、Suzuki Yukio、Sukegawa Akiko、Ikeda Sayaka、Miyagi Etsuko、Enomoto Takayuki、Kimura Tadashi
  • Journal Title: Vaccines Volume: 9 Issue: 11 Pages: 1263-1263
  • DOI: 10.3390/vaccines9111263
• [Journal Article] PET/MR imaging for the evaluation of cervical cancer during pregnancy (2021)
  • Author(s): Ishiguro Tatsuya、Nishikawa Nobumichi、Ishii Shiro、Yoshihara Kosuke、Haino Kazufumi、Yamaguchi Masayuki、Adachi Sosuke、Watanabe Takafumi、Soeda Shu、Enomoto Takayuki
  • Journal Title: BMC Pregnancy and Childbirth Volume: 21 Issue: 1
  • DOI: 10.1186/s12884-021-03766-w
• [Journal Article] Risk factors for HPV infection and high-grade cervical disease in sexually active Japanese women. (2021)
  • Author(s): Yamaguchi M, Sekine M, Hanley SJB, Kudo R, Hara M, Adachi S, Ueda Y, Miyagi E, Enomoto T.
  • Journal Title: Sci Rep. Volume: 3;11(1) Issue: 1 Pages: 2898-2898
  • DOI: 10.1038/s41598-021-82354-6
  • Peer Reviewed / Open Access