Molecular analysis of malignant ascites formation by single-cell RNA-sequencing

• Project/Area Number: 15K06861
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: Mori Seiichi 公益財団法人がん研究会, がんプレシジョン医療研究センター 次世代がん研究シーズ育成プロジェクト, プロジェクトリーダー (10334814)
• Co-Investigator(Kenkyū-buntansha): 加藤 一喜 公益財団法人がん研究会, 有明病院 婦人科, 医長 (80399451) ; 杉山 裕子 公益財団法人がん研究会, 有明病院 細胞診断部, 部長 (80322634)
• Research Collaborator: Rika Nishiko 公益財団法人がん研究会, がんプレシジョン医療研究センター 次世代がん研究シーズ育成プロジェクト, 特任研究助手
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2017: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: １細胞解析 / 漿液性卵巣がん / 悪性腹水 / がん細胞 / 炎症細胞 / 中皮細胞 / 腹水 / 1細胞解析 / 細胞間相互作用 / パスウェイ解析 / 細胞分散 / １細胞発現解析

Outline of Final Research Achievements

Although patients with serous ovarian cancer very often accumulate malignant ascites, the molecular mechanism has not been well elucidated and effective therapeutics against ascites formation has neither been available. In this research, we have been performing basic research to understand the molecular etiology. We have been performing single-cell RNA-seq analyses of ascites constituent cells, such as cancer cells, inflammatory cells, mesothelial cells, for comprehensively understanding the intercellular interaction and intracellular pathway abnormality.

Research Products

• [Journal Article] Pattern of programmed cell death-ligand 1 expression and CD8-positive T-cell infiltration before and after chemoradiotherapy in rectal cancer (2018)
  • Author(s): Ogura Atsushi、Akiyoshi Takashi、Yamamoto Noriko、Kawachi Hiroshi、Ishikawa Yuichi、Mori Seiichi、Oba Koji、Nagino Masato、Fukunaga Yosuke、Ueno Masashi
  • Journal Title: European Journal of Cancer Volume: 91 Pages: 11-20
  • DOI: 10.1016/j.ejca.2017.12.005
  • Peer Reviewed / Open Access
• [Journal Article] Serum miR-143 levels predict the pathological response to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer (2017)
  • Author(s): Hiyoshi Y, Akiyoshi T, Inoue R, Murofushi K, Yamamoto N, Fukunaga Y, Ueno M, Baba H, Mori S, Yamaguchi T
  • Journal Title: Oncotarget Volume: 印刷中 Issue: 45 Pages: 79201-79211
  • DOI: 10.18632/oncotarget.16760
  • Peer Reviewed / Open Access
• [Journal Article] Transposon insertional mutagenesis in mice identifies human breast cancer susceptibility genes and signatures for stratification (2017)
  • Author(s): Chen L, Jenjaroenpun P, Pillai AM, Ivshina AV, Ow GS, Efthimios M, Zhiqun T, Tan TZ, Lee SC, Rogers K, Ward JM, Mori S, Adams DJ, Jenkins NA, Copeland NG, Ban KH, Kuznetsov VA, Thiery JP
  • Journal Title: Proc Natl Acad Sci USA Volume: 114 Issue: 11
  • DOI: 10.1073/pnas.1701512114
  • Peer Reviewed / Open Access / 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] Mouse models for ROS1-fusion-positive lung cancers and their application to the analysis of multikinase inhibitor efficiency. (2016)
  • Author(s): Inoue M, Toki H, Matsui J, Togashi Y, Dobashi A, Fukumura R, Gondo Y, Minowa O, Tanaka N, Mori S, Takeuchi K, Noda T.
  • Journal Title: Carcinogenesis Volume: 0 Pages: 0-0
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Identification of AIM2 as a downstream target of JAK2V617F. (2016)
  • Author(s): Liew EL, Araki M, Hironaka Y, Mori S, Tan TZ, Morishita S, Edahiro Y, Ohsaka A, Komatsu N.
  • Journal Title: Exp Hematol Oncol. Volume: 5 Issue: 1 Pages: 2-2
  • DOI: 10.1186/s40164-016-0032-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] JCA-AACR Joint Symposia in the 73rd Annual Meeting of the Japanese Cancer Association, Yokohama, 25-26 September 2014. (2015)
  • Author(s): Yao R, Mori S, Noda T
  • Journal Title: Cancer Sci. Volume: 106 Issue: 4 Pages: 475-9
  • DOI: 10.1111/cas.12625
  • Peer Reviewed / Open Access
• [Journal Article] Activation of protein phosphatase 2A tumor suppressor as potential treatment of pancreatic cancer. (2015)
  • Author(s): Chien W, Sun QY, Lee KL, Ding LW, Wuensche P, Torres-Fernandez LA, Tan SZ, Tokatly I, Zaiden N, Poellinger L, Mori S, Yang H, Tyner JW, Koeffler HP.
  • Journal Title: Mol Oncol. Volume: 9 Issue: 4 Pages: 889-905
  • DOI: 10.1016/j.molonc.2015.01.002
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Comprehensive sequencing analyses of uterine and ovarian carcinosarcoma (2016)
  • Author(s): Seiichi Mori, Osamu Gotoh, Yuko Sugiyama, Kazuyoshi Kato, Yutaka Takazawa, Tetsuo Noda
  • Organizer: AACR Annual Meeting 2016 in New Orleans, Louisiana
  • Place of Presentation: New Orleans, Louisiana
  • Int'l Joint Research
• [Presentation] Genomic analyses reveal two distinct biologic entities of endometrial endometrioid carcinoma. (2016)
  • Author(s): Yuko Sugiyama, Nobuyuki Fukui, Osamu Gotoh, Katsuhiko Hasumi, Yutaka Takazawa, Tetsuo Noda, Seiichi Mori
  • Organizer: AACR Annual Meeting 2016 in New Orleans, Louisiana
  • Place of Presentation: New Orleans, Louisiana
  • Int'l Joint Research
• [Presentation] Two distinct tumorigenic processes of endometrial endometrioid adenocarcinoma (2016)
  • Author(s): Sugiyama Y, Fukui N,.Gotoh O, Hasumi K, Takazawa Y, Noda T, Mori S.
  • Organizer: 第75回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] 子宮・卵巣がん肉腫の包括的ターゲットリシーケンス解析 (2016)
  • Author(s): 後藤 理, 杉山 裕子, 竹島 信宏, 高澤 豊, 長谷川 幸清, 藤原 恵一, 野田 哲生, 森 誠一
  • Organizer: 第75回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] 難治性婦人科がんにおけるゲノミクスを用いた分子標的・バイオマーカーの探索 (2015)
  • Author(s): 森 誠一
  • Organizer: 第53回日本癌治療学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2015-10-28
  • Invited