Comprehensive metabolomics among tumor-related genes

• Project/Area Number: 26861324
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Kyoto University
• Principal Investigator: Yamaguchi Ken 京都大学, 医学(系)研究科(研究院), 助教 (20378772)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 卵巣癌 / エピジェネティック / 代謝 / 明細胞癌 / SWI/SNF複合体

Outline of Final Research Achievements

Ovarian clear cell carcinoma (CCC) is a histologic subtype of epithelial ovarian cancer (EOC) with unique characteristics including chemoresistance and carcinogenic origins from endometriotic cysts. We identified that HNF1B which is expressing highly in CCC contributes to proliferation in the stress environment. HNF1B also affects the chemoresistance through Warburg effect and glutathione synthesis. ARID1A is a subunit of SWI/SNF complex. Although ARID1A expression was not related to poor prognosis, the SWI/SNF-negative group exhibited significantly shorter progression-free and overall survival (p<0.05). Multivariate analysis suggested that SWI/SNF complex expression status was an independent prognostic factor.

Research Products

• [Journal Article] Prediction of taxane and platinum sensitivity in ovarian cancer based on gene expression profiles. (2016)
  • Author(s): Murakami R, Matsumura N, Brown JB, Wang Z, Yamaguchi K, Abiko K, Yoshioka Y, Hamanishi J, Baba T, Koshiyama M, Mandai M, Yamada R, Konishi I.
  • Journal Title: Gynecol Oncol. Volume: 141 Issue: 1 Pages: 49-56
  • DOI: 10.1016/j.ygyno.2016.02.027
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Establishment of a Novel Histopathological Classification of High-Grade Serous Ovarian Carcinoma Correlated with Prognostically Distinct Gene Expression Subtypes. (2016)
  • Author(s): Murakami R, Matsumura N, Mandai M, Yoshihara K, Tanabe H, Nakai H, Yamanoi K, Abiko K, Yoshioka Y, Hamanishi J, Yamaguchi K, Baba T, Koshiyama M, Enomoto T, Okamoto A, Murphy SK, Mori S, Mikami Y, Minamiguchi S, Konishi I
  • Journal Title: Am J Pathol. Volume: 186 Issue: 5 Pages: 1103-13
  • DOI: 10.1016/j.ajpath.2015.12.029
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical efficacy of neoadjuvant chemotherapy with irinotecan (CPT-11) and nedaplatin followed by radical hysterectomy for locally advanced cervical cancer. (2016)
  • Author(s): Abou-Taleb HA, Koshiyama M, Matsumura N, Baba T, Yamaguchi K, Hamanishi J, Abiko K, Yamanoi K, Murakami R, Horikawa N, Taha AA, Kitamura S, Konishi I.
  • Journal Title: J Int Med Res. Volume: 44 Issue: 2 Pages: 346-356
  • DOI: 10.1177/0300060515591858
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Chemotherapy Induces Programmed Cell Death-Ligand 1 Overexpression via the Nuclear Factor-κB to Foster an Immunosuppressive Tumor Microenvironment in Ovarian Cancer. (2015)
  • Author(s): Peng J, Hamanishi J, Matsumura N, Abiko K, Murat K, Baba T, Yamaguchi K, Horikawa N, Hosoe Y, Murphy SK, Konishi I, Mandai M.
  • Journal Title: Cancer Res. Volume: 75 Issue: 23 Pages: 5034-5045
  • DOI: 10.1158/0008-5472.can-14-3098
  • Peer Reviewed
• [Journal Article] Genomic profile predicts the efficacy of neoadjuvant chemotherapy for cervical cancer patients. (2015)
  • Author(s): Horikawa N, Baba T, Matsumura N, Murakami R, Abiko K, Hamanishi J, Yamaguchi K, Koshiyama M, Yoshioka Y, Konishi I.
  • Journal Title: BMC Cancer. Volume: 15 Issue: 1 Pages: 739-739
  • DOI: 10.1186/s12885-015-1703-1
  • NAID: 120005749961
  • Peer Reviewed / Open Access
• [Journal Article] Safety and Anti-tumor Activity of Anti&#8211;PD-1 Antibody (Nivolumab: ONO-4538/BMS-936558) in Patients with Platinum-resistant Ovarian Cancer. (2015)
  • Author(s): Hamanishi, J., M. Mandai, T. Ikeda, M. Minami, A. Kawaguchi, T. Murayama, M. Kanai, Y. Mori, S. Matsumoto, S. Chikuma, N. Matsumura, K. Abiko, T. Baba, K. Yamaguchi, A. Ueda, Y. Hosoe, S. Morita, M. Yokode, A. Shimizu, T. Honjo, I. Konishi.
  • Journal Title: J Clin Oncol Volume: 33 Issue: 34 Pages: 4015-22
  • DOI: 10.1200/jco.2015.62.3397
  • Peer Reviewed / Open Access
• [Journal Article] Metabolic alterations caused by HNF1β expression in ovarian clear cell carcinoma contribute to cell survival. (2015)
  • Author(s): Amano Y, Mandai M, Yamaguchi K, Matsumura N, Kharma B, Baba T, Abiko K, Hamanishi J, Yoshioka Y, Konishi I.
  • Journal Title: Oncotarget. Volume: 6 Issue: 28 Pages: 26002-26017
  • DOI: 10.18632/oncotarget.4692
  • Peer Reviewed
• [Journal Article] IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer (2015)
  • Author(s): Abiko K, Matsumura N, Hamanishi J, Horikawa N, Murakami R, Yamaguchi K, Yoshioka Y, Baba T, Konishi I, Mandai M
  • Journal Title: British Journal of Cancer Volume: 未確定 Issue: 9 Pages: 1501-1509
  • DOI: 10.1038/bjc.2015.101
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The BMP signaling pathway leads to enhanced proliferation in serous ovarian cancer-a potential therapeutic target. (2015)
  • Author(s): Peng J, Yoshioka Y, Mandai M, et al
  • Journal Title: Mol Carcinog Volume: Epub ahead of print Issue: 4 Pages: 1-11
  • DOI: 10.1002/mc.22283
  • Peer Reviewed / Open Access
• [Journal Article] Invasion of uterine cervical squamous cell carcinoma cells is facilitated by locoregional interaction with cancer-associated fibroblasts via activating transforming growth factor-beta. (2015)
  • Author(s): Nagura M, Matsumura N, Baba T, Murakami R, Kharma B, Hamanishi J, Yamaguchi K, Abiko K, Koshiyama M, Mandai M, et al.
  • Journal Title: Gynecol Oncol Volume: 136 Issue: 1 Pages: 104-111
  • DOI: 10.1016/j.ygyno.2014.11.075
  • Peer Reviewed / Open Access
• [Journal Article] Menstrual cyclic change of metastin/GPR54 in endometrium. (2014)
  • Author(s): Baba T, Kang HS, Hosoe Y, Kharma B, Abiko K, Matsumura N, Hamanishi J, Yamaguchi K, Yoshioka Y, Koshiyama M, Mandai M, Murphy SK, Konishi I.
  • Journal Title: Med Mol Morphol Volume: Epub ahead of print Pages: 1-9
  • Peer Reviewed / Open Access
• [Journal Article] STAT1 drives tumor progression in serous papillary endometrial cancer. (2014)
  • Author(s): Kharma B, Baba T, Matsumura N, Kang HS, Hamanishi J, Murakami R, McConechy MM, Leung S, Yamaguchi K, Hosoe Y, Yoshioka Y, Murphy SK, Mandai M, Huntsman DG, Konishi I.
  • Journal Title: Cancer Res. Volume: 74 Issue: 22 Pages: 6519-6530
  • DOI: 10.1158/0008-5472.can-14-0847
  • Peer Reviewed / Open Access
• [Journal Article] Clinical approaches to treating papillary squamous cell carcinoma of the uterine cervix. (2014)
  • Author(s): Nagura M, Koshiyama M, Matsumura N, Kido A, Baba T, Abiko K, Hamanishi J, Yamaguchi K, Mikami Y, Konishi I.
  • Journal Title: BMC Cancer Volume: 14 Issue: 1 Pages: 784-784
  • DOI: 10.1186/1471-2407-14-784
  • Peer Reviewed / Open Access
• [Journal Article] Clear cell carcinoma arising from a uterus-like mass. (2014)
  • Author(s): Nakakita B, Abiko K, Mikami Y, Kido A, Baba T, Yoshioka Y, Yamaguchi K, Matsumura N, Konishi I.
  • Journal Title: Pathol Int Volume: 64 Issue: 11 Pages: 576-580
  • DOI: 10.1111/pin.12218
  • Peer Reviewed / Open Access
• [Journal Article] Epigenetic and genetic dispositions of ovarian carcinomas. (2014)
  • Author(s): Yamaguchi K, Matsumura N, Mandai M, Baba T, Konishi I, Murphy SK.
  • Journal Title: Oncoscience Volume: 1 Pages: 574-579
  • Peer Reviewed / Open Access
• [Journal Article] Epigenetic determinants of ovarian clear cell carcinoma biology. (2013)
  • Author(s): Yamaguchi K, Huang Z, Matsumura N, Mandai M, Okamoto T, Baba T, Konishi I, Berchuck A, Murphy SK.
  • Journal Title: Int J Cancer. Volume: - Issue: 3 Pages: 585-97
  • DOI: 10.1002/ijc.28701
  • Peer Reviewed / Open Access
• [Presentation] Genomic Alterations of Ovarian Clear Cell Carcinoma (2015)
  • Author(s): Noriomi Matsumura
  • Organizer: The 57th meeting of the Japan Society of Gynecologic Oncology
  • Place of Presentation: アイーナ岩手県民情報センター(盛岡市)
  • Year and Date: 2015-08-07
  • Invited
• [Presentation] 卵巣明細胞癌におけるSWI/SNF複合体の網羅的遺伝子変異解析 (2015)
  • Author(s): 山口 建
  • Organizer: 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(横浜市)
  • Year and Date: 2015-04-09
• [Presentation] Oxidative Stress and Metabolic Regulation in Clear Cell Carcinoma: Ovarian clear cell carcinoma is metabolic disease regulated epigenetically in the stressful carcinogenic environments (2014)
  • Author(s): Ken Yamaguchi
  • Organizer: 15th Biennial meeting of the International Gynecologic Cancer Society
  • Place of Presentation: メルボルン
  • Year and Date: 2014-11-08 – 2014-11-14
  • Invited
• [Presentation] Loss of SWI/SNF chromatin-remodeling complex is a prognostic biomarker in ovarian clear cell carcinoma (2014)
  • Author(s): 山口建、アブタレブヒシャム、松村謙臣、天野泰彰、山ノ井康二、村上隆介、安彦郁、吉岡弓子、濱西潤三、越山雅文、馬場長、小西郁生
  • 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] 卵巣明細胞腺癌の形質は、ストレス発癌環境の中でエピジェネテックにより制御された代謝異常である (2014)
  • Author(s): 山口 建、天野 泰彰、松村 謙臣、Hisham Abou-Taleb、山ノ井 康二、村上 隆介、安彦 郁、吉岡 弓子、濱西 潤三、越山 雅文、馬場 長、万代 昌紀、小西 郁生
  • Organizer: 第1回新潟産婦人科シンポジウム
  • Place of Presentation: 新潟
  • Year and Date: 2014-09-14
  • Invited
• [Presentation] 卵巣明細胞腺癌においてSWI/SNF複合体は予後因子である (2014)
  • Author(s): 山口建、ヒシャムアブタレブ、松村謙臣、天野泰彰、山ノ井康二、村上隆介、安彦郁、吉岡弓子、濱西潤三、越山雅文、馬場長、小西郁生
  • Organizer: 第56回日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 栃木総合文化センター
  • Year and Date: 2014-07-17 – 2014-07-19
• [Presentation] SWI/SNF複合体因子の発現消失は卵巣明細胞腺癌の予後を予測するバイオマーカーとなる (2014)
  • Author(s): 山口建、Hisham Abou Taleb、松村謙臣、村上隆介、山ノ井康二、天野泰彰、安彦郁、吉岡弓子、濱西潤三、越山雅文、馬場長、小西郁生
  • Organizer: 第2回婦人科がんバイオマーカー研究会学術集会
  • Place of Presentation: 東京慈恵医科大学
  • Year and Date: 2014-07-05
• [Presentation] Role of SWI/SNF complex in Clear Cell Carcinoma of the ovary (CCC) (2014)
  • Author(s): Ken Yamaguchi, Hisham Abou-Taleb, Noriomi Matsumura, Yasuaki Amano, Koji Yamanoi, Ryusuke Murakami, Tsukasa Baba, Yumiko Yoshioka, Junzo Hamanishi, Masaki Mandai, Ikuo Konishi
  • 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
• [Book] 産婦人科の実際 (2014)
  • Author(s): 万代昌紀、山口建、岡本尊子、松村謙臣、小西郁生
  • Publisher: 金原出版