Identification of pancreatic cancer specific metabolites by metabolome mapping and application possibility for diagnostic biomarker.

• Project/Area Number: 26462066
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: TORATA Nobuhiro 九州大学, 大学病院, 臨床検査技師 (00398075)
• Co-Investigator(Kenkyū-buntansha): 前山 良 九州大学, 医学研究院, 共同研究員 (10611668) ; 三浦 大典 九州大学, 先端融合医療レドックスナビ研究拠点, 准教授 (40532627) ; 真鍋 達也 九州大学, 大学病院, 講師 (60546464)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: MALDI-MSI / Energy Charge / 凍結組織アレイ / バイオマーカー探索

Outline of Final Research Achievements

Six frozen tissue microarray(fTMA)blocks were constructed using 119 breast tissue sections from 99 patients, carcinoma, normal areas of individual tissues were confirmed by histology. We detected 1,915 endogenous metabolite peaks by direct tissue MALDI-MSI analysis of breast carcinoma fTMAs. Among them,185 commonly detected peaks were subjected to further analysis,and 88.6% of peaks from carcinoma tissues were significantly different, 92.7% of which showed higher than normal intensities. We further identified 18 metabolites related to energy metabolism such as ATP. Comparing metabolite profiles from carcinoma and normal tissues, we found that the EC and the sum of AXP were significantly higher in cancerous tissues than normal tissues, but there were no significant differences between lymph node metastasis, histological type or tumor size. Comparing tumor subtypes, a higher EC was observed in ER+/HER2- tumors than other subtypes, but AXP showed no significant differences among subtypes.

Research Products

• [Journal Article] Role of Ad4-binding protein/steroidogenic factor 1 in regulating NADPH production in adrenocortical Y-1 cells (2017)
  • Author(s): Li B, BabaT, Miyabayashi K, Sato T, Shima Y, Ichinose T, Miura D, Ohkawa Y, Suyama M, Morohashi KI
  • Journal Title: Endocrine Journal Volume: 64 Issue: 3 Pages: 315-324
  • DOI: 10.1507/endocrj.EJ16-0467
  • NAID: 130005529460
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] Extra-pancreatic invasion induces lipolytic and fibrotic changes in the adipose microenvironment, with released fatty acids enhancing the invasiveness of pancreatic cancer cells. (2017)
  • Author(s): Okumura T, Ohuchida K, Sada M, Abe T, Endo S, Koikawa K, Iwamoto C, Miura D, Mizuuchi Y, Moriyama T, Nakata K, Miyasaka Y, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Oda Y, Hashizume M, Nakamura M.
  • Journal Title: Oncotarget Volume: 8 Issue: 11 Pages: 18280-18295
  • DOI: 10.18632/oncotarget.15430
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Spatially resolved metabolic distribution for unraveling the physiological change and responses in tomato fruit using matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) (2017)
  • Author(s): Nakamura J, Morikawa-Ichinose T, Fujimura Y, Hayakawa E, Takahashi K, Ishii T, Miura D, and Wariishi H
  • Journal Title: Anal Bioanal Chem Volume: 409 Issue: 6 Pages: 1697-1706
  • DOI: 10.1007/s00216-016-0118-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Plasma Metabolites Predict Severity of Depression and Suicidal Ideation in Psychiatric Patients-A Multicenter Pilot Analysis (2016)
  • Author(s): Setoyama D, Kato TA, Hashimoto R, Kunugi H, Hattori K, Hayakawa K, Sato-Kasai M, Shimokawa N, Kaneko S, Yoshida S, Goto YI, Yasuda Y, Yamamori H, Ohgidani M, Sagata N, Miura D, Kang D, Kanba S
  • Journal Title: PLoS ONE Volume: 11(12) Issue: 12 Pages: e0165267-e0165267
  • DOI: 10.1371/journal.pone.0165267
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] MSIdV: a versatile tool to visualize biological indices from mass spectrometry imaging data. (2016)
  • Author(s): Hayakawa E, Fujimura Y, Miura D.
  • Journal Title: Bioinformatics. Volume: 32 Pages: 3852-3854
  • Peer Reviewed
• [Journal Article] TM4SF1 as a prognostic marker of pancreatic ductal adenocarcinoma is involved in migration and invasion of cancer cells (2015)
  • Author(s): Zheng B, Ohuchida K, Cui L, Zhao M, Shindo K, Fujiwara K, Manabe T, Torata N, Moriyama T, Miyasaka Y, Ohtsuka T, Takahata S, Mizumoto K, Oda Y, Tanaka M
  • Journal Title: Int J Oncol. Volume: 47 Issue: 2 Pages: 490-498
  • DOI: 10.3892/ijo.2015.3022
  • Peer Reviewed
• [Journal Article] Metabolic Profiling-based Data-mining for an Effective Chemical Combination to Induce Apoptosis of Cancer Cells. (2015)
  • Author(s): Kumazoe M, Fujimura Y, Hidaka S, Kim Y, Murayama K, Takai M, Huang Y, Yamashita S, Murata M, Miura D, Wariishi H, Maeda-Yamamoto M, Tachibana H.
  • Journal Title: Sci Rep. Volume: 31 Issue: 1 Pages: 9474-9474
  • DOI: 10.1038/srep09474
  • Peer Reviewed / Open Access
• [Journal Article] Sphingosine kinase-1 protects multiple myeloma from apoptosis driven by cancer specific inhibition of RTKs. (2015)
  • Author(s): Tsukamoto S, Huang Y, Kumazoe M, Lesnick C, Yamada S, Ueda N, Suzuki T, Yamashita S, Kim YH, Fujimura Y, Miura D, Kay NE, Shanafelt TD, Tachibana H.
  • Journal Title: Mol Cancer Ther. Volume: 14 Issue: 10 Pages: 2303-2312
  • DOI: 10.1158/1535-7163.mct-15-0185
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tissue tablet method: an efficient tissue banking procedure applicable to both molecular analysis and frozen tissue microarray (2014)
  • Author(s): Torata N, Ohuchida K, Akagawa S, Cui L, Kozono S, Mizumoto K, Aishima S, Oda Y, Tanaka M
  • Journal Title: Hum Pathol Volume: 45 Issue: 1 Pages: 143-152
  • DOI: 10.1016/j.humpath.2013.08.013
  • Peer Reviewed
• [Presentation] MALDI mass spectrometry imaging profile of low molecular metabolites in breast carcinoma tissues embedded in frozen tissue microarray (2015)
  • Author(s): Torata N,Kubo M,Miura D,Ohuchida K,Miyazaki T,Fujimura Y,Hayakawa E,Kai M,Oda Y,Mizumoto K,Hashizume M,Nakamura M
  • Organizer: San Antonio Breast Cancer Symposium 2015
  • Place of Presentation: San Antonio(USA)
  • Year and Date: 2015-12-06
  • Int'l Joint Research
• [Presentation] MALDI mass spectrometry imagingによる凍結組織アレイ包埋乳がん組織の低分子代謝産物プロファイリング (2015)
  • Author(s): 寅田信博、久保 真、三浦大典、大内田研宙、宮崎哲之、藤村由紀、早川英介、大塚 隆生、宮坂義浩、真鍋達也、小田義直、水元一博、中村雅史
  • Organizer: 第40回日本医用マススペクトル学会年会
  • Place of Presentation: 浜松市
  • Year and Date: 2015-09-17
• [Presentation] MALDI-MS-based metabolite analysis for biomarker discovery and diagnosis. (2014)
  • Author(s): Daisuke Miura
  • Organizer: RERF symposium “Application of ‘omics’ to Radiation Research”
  • Place of Presentation: 広島市
  • Year and Date: 2014-12-03
• [Presentation] MALDI-MS-based metabolite analysis for biomarker discovery and diagnosis. (2014)
  • Author(s): Daisuke Miura
  • Organizer: CIS workshop “Mass spectrometry for proteomics and imaging”
  • Place of Presentation: 札幌市
  • Year and Date: 2014-10-24
• [Presentation] MALDI-MS-based metabolomic imaging technique and its application to pathological analysis (2014)
  • Author(s): Daisuke Miura
  • Organizer: DFG-JSPS Symposium “SHARED PATHWAYS IN CNS SIDORDERS”
  • Place of Presentation: Munich, Germany
  • Year and Date: 2014-06-30
• [Presentation] Tissue Tablet法（簡便な凍結組織アレイ作製に対応した高効率手術切除組織保存法）2年間の運用報告 (2014)
  • Author(s): 寅田信博、赤川進、水内祐介、大内田研宙 、水元一博、相島慎一、小田義直、田中 雅夫
  • Organizer: 第103回 日本病理学会
  • Place of Presentation: 広島市
  • Year and Date: 2014-04-25
• [Presentation] 冷凍組織アレイおよび質量分析イメージングをもちいた乳癌における癌関連代謝産物の高効率マッピング実証 (2014)
  • Author(s): 寅田信博、久保真、三浦大典、大内田研宙、水内祐介、藤村美紀、入江美穂、大塚隆生、仲田興平、前山良、宮坂義浩、小田義直、水元一博、田中雅夫
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2014-04-04