Identification and verification of novel biomarkers for clinical renal cell carcinoma bu lipidomics.

• Project/Area Number: 17K07194
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: National Center for Global Health and Medicine (2020); Akita University (2017-2019)
• Principal Investigator: Nakanishi Hiroki 国立研究開発法人国立国際医療研究センター, 研究所, 脂質シグナリングプロジェクト 特任研究員 (10466740)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: バイオマーカー / リピドミクス / 診断 / 腫瘍 / 泌尿器がん / リピドーム解析 / シグナル伝達

Outline of Final Research Achievements

In this study, we investigated lipidome profile in human renal cell carcinoma (RCC) tissues with an original method using mass spectrometry. By correlating with clinical data, we discovered novel biomarker candidates that contribute to the oncological outcome in patients with RCC. In the future, we also aim to become a novel treatment strategy for RCC by analysis of targeting related enzymes.

Academic Significance and Societal Importance of the Research Achievements

本研究は、基礎医学講座で開発された独自の脂質分析技術を実際の臨床検体を用いて解析しており、基礎研究成果の社会還元を図る橋渡し的な位置づけとなる。本研究成果である腎がん術後予後予測の診断候補分子の同定を足がかりに、種々のがん、さらにはより多くの疾患の予防・診断・治療法開発に資する研究基盤の形成につながる。本研究の成果は、新たな医薬品の創製へと繋がる可能性が高く、また、疾患マーカー脂質の発見による早期診断法ならびに術後予後予測法の確立は、国民の健康維持と医療費削減に繋がるなど、経済的・産業的に大きな波及効果も期待される。

Research Products

• [Journal Article] Fatty Acid Synthesis Is Indispensable for Survival of Human Pluripotent Stem Cells (2020)
  • Author(s): Sho Tanosaki, Shugo Tohyama, Jun Fujita, Hiroki Nakanishi, Takayo Ohto-Nakanishi, Tomohiko Akiyama, Yuika Morita, Yoshikazu Kishino, Marina Okada, Hidenori Tani, Yusuke Soma, Kazuaki Nakajima, Hideaki Kanazawa, Masahiro Sugimoto, Minoru S.H. Ko, Makoto Suematsu, Keiichi Fukuda
  • Journal Title: iScience Volume: 23 Issue: 9 Pages: 101535-101535
  • DOI: 10.1016/j.isci.2020.101535
  • Peer Reviewed / Open Access
• [Journal Article] Microglia-released leukotriene B4 promotes neutrophil infiltration and microglial activation following intracerebral hemorrhage. (2020)
  • Author(s): Hijioka M, Futokoro R, Ohto-Nakanishi T, Nakanishi H, Katsuki H, Kitamura Y.
  • Journal Title: Int Immunopharmacol. Volume: 85 Pages: 106678-106678
  • DOI: 10.1016/j.intimp.2020.106678
  • Peer Reviewed / Open Access
• [Journal Article] Polarized PtdIns(4,5)P2distribution mediated by a voltage-sensing phosphatase (VSP) regulates sperm motility (2019)
  • Author(s): Kawai Takafumi、Miyata Haruhiko、Nakanishi Hiroki、Sakata Souhei、Morioka Shin、Sasaki Junko、Watanabe Masahiko、Sakimura Kenji、Fujimoto Toyoshi、Sasaki Takehiko、Ikawa Masahito、Okamura Yasushi
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 116 Issue: 51 Pages: 26020-26028
  • DOI: 10.1073/pnas.1916867116
  • Peer Reviewed / Open Access
• [Journal Article] Inter-laboratory comparison of metabolite measurements for metabolomics data integration (2019)
  • Author(s): Izumi Yoshihiro、Matsuda Fumio、Hirayama Akiyoshi、Ikeda Kazutaka、Kita Yoshihiro、Horie Kanta、Saigusa Daisuke、Saito Kosuke、Sawada Yuji、Nakanishi Hiroki、Okahashi Nobuyuki、Takahashi Masatomo、Nakao Motonao、Hata Kosuke、Hoshi Yutaro、Morihara Motohiko、Tanabe Kazuhiro、Bamba Takeshi、Oda Yoshiya
  • Journal Title: Metabolites Volume: 9 Issue: 11 Pages: 257-257
  • DOI: 10.3390/metabo9110257
  • URL: https://pure.teikyo.jp/en/publications/0579b4df-6bc3-4f95-959c-a79f4972d795
  • Peer Reviewed / Open Access
• [Journal Article] Increased fatty acyl saturation of phosphatidylinositol phosphates in prostate cancer progression (2019)
  • Author(s): Koizumi Atsushi、Narita Shintaro、Nakanishi Hiroki、Ishikawa Masaki、Eguchi Satoshi、Kimura Hirotaka、Takasuga Shunsuke、Huang Mingguo、Inoue Takamitsu、Sasaki Junko、Yoshioka Toshiaki、Habuchi Tomonori、Sasaki Takehiko
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 13257-13257
  • DOI: 10.1038/s41598-019-49744-3
  • Peer Reviewed / Open Access
• [Journal Article] Sirt1 counteracts decrease in membrane phospholipid unsaturation and diastolic dysfunction during saturated fatty acid overload (2019)
  • Author(s): Yamamoto Tsunehisa、Endo Jin、Kataoka Masaharu、Matsuhashi Tomohiro、Katsumata Yoshinori、Shirakawa Kohsuke、Yoshida Naohiro、Isobe Sarasa、Moriyama Hidenori、Goto Shinichi、Yamashita Kaoru、Ohto-Nakanishi Takayo、Nakanishi Hiroki、Shimanaka Yuta、Kono Nozomu、Shinmura Ken、Arai Hiroyuki、Fukuda Keiichi、Sano Motoaki
  • Journal Title: Journal of Molecular and Cellular Cardiology Volume: 133 Pages: 1-11
  • DOI: 10.1016/j.yjmcc.2019.05.019
  • Peer Reviewed / Open Access
• [Journal Article] Basal expression of interferon regulatory factor 1 drives intrinsic hepatocyte resistance to multiple RNA viruses (2019)
  • Author(s): Yamane D, Feng H, Rivera-Serrano EE, Selitsky SR, Hirai-Yuki A, Das A, McKnight KL, Misumi I, Hensley L, Lovell W, González-López O, Suzuki R, Matsuda M, Nakanishi H, Ohto-Nakanishi T, Hishiki T, Wauthier E, Oikawa T, Morita K, Reid LM, Sethupathy P, Kohara M, Whitmire JK, Lemon SM
  • Journal Title: Nature Microbiology Volume: 印刷中 Issue: 7 Pages: 1096-1104
  • DOI: 10.1038/s41564-019-0425-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lysophosphatidylinositol‐acyltransferase‐1 is involved in cytosolic Ca2+ oscillations in macrophages (2019)
  • Author(s): Takemasu Shinya、Ito Masaki、Morioka Shin、Nigorikawa Kiyomi、Kofuji Satoshi、Takasuga Shunsuke、Eguchi Satoshi、Nakanishi Hiroki、Matsuoka Isao、Sasaki Junko、Sasaki Takehiko、Hazeki Kaoru
  • Journal Title: Genes to Cells Volume: - Issue: 5 Pages: 1-11
  • DOI: 10.1111/gtc.12681
  • Peer Reviewed / Open Access
• [Journal Article] Decrease in membrane phospholipids unsaturation correlates with myocardial diastolic dysfunction (2018)
  • Author(s): Yamamoto Tsunehisa、Endo Jin、Kataoka Masaharu、Matsuhashi Tomohiro、Katsumata Yoshinori、Shirakawa Kohsuke、Yoshida Naohiro、Isobe Sarasa、Moriyama Hidenori、Goto Shinichi、Yamashita Kaoru、Nakanishi Hiroki、Shimanaka Yuta、Kono Nozomu、Shinmura Ken、Arai Hiroyuki、Fukuda Keiichi、Sano Motoaki
  • Journal Title: PLOS ONE Volume: 13 Issue: 12 Pages: 0208396-0208396
  • DOI: 10.1371/journal.pone.0208396
  • URL: https://localhost/en/publications/c494d8bc-a57b-4e2e-9922-c30bd4e08d67
  • Peer Reviewed / Open Access
• [Journal Article] Loss of DDHD2, whose mutation causes spastic paraplegia, promotes reactive oxygen species generation and apoptosis (2018)
  • Author(s): Maruyama Tomohiro、Baba Takashi、Maemoto Yuki、Hara-Miyauchi Chikako、Hasegawa-Ogawa Minami、Okano Hirotaka James、Enda Yuki、Matsumoto Kei、Arimitsu Nagisa、Nakao Kazuki、Hamamoto Hiroshi、Sekimizu Kazuhisa、Ohto-Nakanishi Takayo、Nakanishi Hiroki、Tokuyama Takeshi、Yanagi Shigeru、Tagaya Mitsuo、Tani Katsuko
  • Journal Title: Cell Death & Disease Volume: 9 Issue: 8 Pages: 797-811
  • DOI: 10.1038/s41419-018-0815-3
  • URL: https://pure.teikyo.jp/en/publications/52ddd73e-02a1-4739-b369-a9248e11590b
  • Peer Reviewed / Open Access
• [Journal Article] Metabolic determinants of sensitivity to phosphatidylinositol 3-kinase pathway inhibitor in small-cell lung carcinoma (2018)
  • Author(s): Makinoshima H et al.
  • Journal Title: Cancer Research Volume: - Issue: 9 Pages: 2179-2190
  • DOI: 10.1158/0008-5472.can-17-2109
  • Peer Reviewed / Open Access
• [Journal Article] TMEM55a localizes to macrophage phagosomes to downregulate phagocytosis (2018)
  • Author(s): Morioka Shin、Nigorikawa Kiyomi、Okada Eri、Tanaka Yoshimasa、Kasuu Yoshihiro、Yamada Miho、Kofuji Satoshi、Takasuga Shunsuke、Nakanishi Hiroki、Sasaki Takehiko、Hazeki Kaoru
  • Journal Title: Journal of Cell Science Volume: 131 Issue: 5 Pages: 213272-213272
  • DOI: 10.1242/jcs.213272
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] PTEN Regulates PI(3,4)P 2 Signaling Downstream of Class I PI3K (2017)
  • Author(s): Malek M、Kielkowska A、Chessa T、Anderson K E.、Barneda D、Pir P、Nakanishi H、Eguchi S、Koizumi A、Sasaki J、Juvin V、Kiselev VY.、Niewczas I、Gray A、Valayer A、Spensberger D、Imbert M、Felisbino S、Habuchi T、Beinke S、Cosulich S、Le Novere N、Sasaki T、Clark J、Hawkins PT.、Stephens LR.
  • Journal Title: Molecular Cell Volume: 68 Issue: 3 Pages: 566-580
  • DOI: 10.1016/j.molcel.2017.09.024
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The effect and possible clinical efficacy of in vivo inhibition of neutrophil extracellular traps by blockade of PI3K-gamma on the pathogenesis of microscopic polyangiitis (2017)
  • Author(s): Kimura Hirotaka、Matsuyama Yasushi、Araki Sachiko、Koizumi Atsushi、Kariya Yumi、Takasuga Shunsuke、Eguchi Satoshi、Nakanishi Hiroki、Sasaki Junko、Sasaki Takehiko
  • Journal Title: Modern Rheumatology Volume: 28 Issue: 3 Pages: 530-541
  • DOI: 10.1080/14397595.2017.1367116
  • Peer Reviewed / Open Access
• [Journal Article] Docosahexaenoic acid preserves visual function by maintaining correct disc morphology in retinal photoreceptor cells (2017)
  • Author(s): Shindou Hideo、Koso Hideto、Sasaki Junko、Nakanishi Hiroki、Sagara Hiroshi、Nakagawa Koh M.、Takahashi Yoshikazu、Hishikawa Daisuke、Iizuka-Hishikawa Yoshiko、Tokumasu Fuyuki、Noguchi Hiroshi、Watanabe Sumiko、Sasaki Takehiko、Shimizu Takao
  • Journal Title: Journal of Biological Chemistry Volume: 292 Issue: 29 Pages: 12054-12064
  • DOI: 10.1074/jbc.m117.790568
  • Peer Reviewed / Open Access
• [Journal Article] Lysophosphatidic acid acyltransferase 3 tunes the membrane status of germ cells by incorporating docosahexaenoic acid during spermatogenesis (2017)
  • Author(s): Iizuka-Hishikawa Yoshiko、Hishikawa Daisuke、Sasaki Junko、Takubo Keiyo、Goto Motohito、Nagata Katsuyuki、Nakanishi Hiroki、Shindou Hideo、Okamura Tadashi、Ito Chizuru、Toshimori Kiyotaka、Sasaki Takehiko、Shimizu Takao
  • Journal Title: Journal of Biological Chemistry Volume: 292 Issue: 29 Pages: 12065-12076
  • DOI: 10.1074/jbc.m117.791277
  • Peer Reviewed / Open Access
• [Presentation] リピドミクス技術を活用したシグナル伝達脂質の新展開 (2019)
  • Author(s): 中西広樹
  • Organizer: 第124回日本解剖学会総会・全国学術集会