Prediction of malignant phenotype using metabolome analysis in gastric cancer

• Project/Area Number: 25462042
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Shizuoka Cancer Center Research Institute
• Principal Investigator: Terashima Masanori 静岡県立静岡がんセンター(研究所), その他部局等, その他 (40197794)
• Co-Investigator(Kenkyū-buntansha): Oshima Keiichi 静岡県立静岡がんセンター, 研究所, 研究員 (10399587) ; Kusuhara Masatoshi 静岡県立静岡がんセンター, 研究所, 研究員 (40169991)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); 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); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: メタボローム解析 / miRNA / splicing variant / whole exome sequence / whole exam sequence / whole exome sequencing

Outline of Final Research Achievements

Metabolome analysis using CE-TOFMS and LC-TOFMS methods in tumor and corresponding normal tissue was performed from in 185 advanced gastric cancers. The concentration of lactate was significantly higher in tumor tissue suggesting that the Warburg effect is predominantly observed in tumor. In addition, the levels of ATP and GTP were lower and most of the level of metabolite from glycolysis showed intermediate level between normal tissue and differentiated type in undifferentiated type. It is suggested that metbolomic profile is quite different between differentiated type and undifferentiated type.
Whole exam analysis and comprehensive expression analysis were performed in 188 gastric cancer. Classification according to Asian Cancer Research Group (ACRG) ws possible. We classified 21 in MSI, 22 in EMT, 15 in TP53+ and 130 in TP53-. Relapse-free survival was significantly worse in EMT and TP53+ patients.

Research Products

• [Journal Article] Robotic surgery for gastric cancer. (2015)
  • Author(s): Terashima M , Tokunaga M, Tanizawa Y, Bando E, Kawamura T, Miki Y, Makuuchi R, Honda S, Tatsubayashi T, Takagi W, Omori H, Hirata F.
  • Journal Title: Gastric Cancer Volume: 18 Issue: 3 Pages: 449-457
  • DOI: 10.1007/s10120-015-0501-4
  • NAID: 40020581259
  • Peer Reviewed
• [Journal Article] Late phase II study of robot-assisted gastrectomy with nodal dissection for clinical stage I gastric cancer. (2015)
  • Author(s): Tokunaga M, Makuuchi R , Miki Y , Tanizawa Y , Bando E , Kawamura T, Terashima M
  • Journal Title: Surgical Endoscopy Volume: 0 Issue: 8 Pages: 0-0
  • DOI: 10.1007/s00464-015-4613-z
  • Peer Reviewed
• [Journal Article] Staging Laparoscopy for Patients with cM0,Type 4,and Large Type 3 Gastric Cancer. (2015)
  • Author(s): Miki Y, Tokunaga M, Tanizawa Y , Bando E, Kawamura T, Terashima M
  • Journal Title: World Journal of Surgery Volume: 39 Issue: 11 Pages: 2742-2747
  • DOI: 10.1007/s00268-015-3144-z
  • Peer Reviewed
• [Journal Article] Risk Classification using the Ki-67 Labeling Index for Surgically-Treated Gastric Gastrointestinal Stromal Tumors. (2015)
  • Author(s): Miki Y, Kawamura T, Sugisawa N, Makuuchi R, Nakajima T, Tokunaga M, Tanizawa Y, Bando E, Terashima M
  • Journal Title: Hepato-gastroenterology Volume: 62 Pages: 919-923
  • Peer Reviewed
• [Journal Article] Postgastrectomy Syndrome Assessment Scale (PGSAS)-45 and Changes in Body Weight are Useful Tools for Evaluation of Reconstruction Methods Following Distal Gastrectomy (2014)
  • Author(s): Terashima M, Tanabe K, Yoshida M, Kawahira H, Inada T, Okabe H, Urushihara T,Kawashima Y, Fukushima N, Nakada K
  • Journal Title: Ann. Surg. Oncol Volume: 21,Suppl. 3 Issue: S3 Pages: 370-378
  • DOI: 10.1245/s10434-014-3583-z
  • Peer Reviewed
• [Journal Article] Survival analysis of adjuvant chemotherapy with S-1 plus cisplatin for stage III gastric cancer. (2014)
  • Author(s): Takahari D, Hamaguchi T, Yoshimura K, Katai H, Ito S, Fuse N, Konishi M, Yasui H, Terashima M, Goto M, Tanigawa N, Shirao K, Sano T, Sasako M.
  • Journal Title: Gastric Cancer Volume: 17 Issue: 2 Pages: 383-386
  • DOI: 10.1007/s10120-013-0264-8
  • Peer Reviewed
• [Journal Article] The optimal extent of lymph node dissection for adenocarcinoma of the esophagogastric junction differs between Siewert type II and Siewert type III patients. (2014)
  • Author(s): Goto H, Tokunaga M, Miki Y, Makuuchi R, Sugisawa N, Tanizawa Y, Bando E, Kawamura T, Niihara M, Tsubosa Y, Terashima M.
  • Journal Title: Gastric Cancer Volume: 未
  • Peer Reviewed
• [Journal Article] Perioperative Risk Assessment for Gastrectomy by Surgical Apgar Score (2014)
  • Author(s): Miki Y, Tokunaga M, Tanizawa Y, Bando E, Kawamura T, Terashima M.
  • Journal Title: Ann Surg Oncol Volume: 未
  • Peer Reviewed
• [Journal Article] Sentinel node mapping for gastric cancer: a prospective multicenter trial in Japan (2013)
  • Author(s): Kitagawa Y, Takeuchi H, Takagi Y, Natsugoe S, Terashima M, Murakami N, Fujimura T, Tsujimoto H, Hayashi H, Yoshimizu N, Takagane A, Mohri Y, Nabeshima K, Uenosono Y, Kinami S, Sakamoto J, Morita S, Aikou T, Miwa K, Kitajima M.
  • Journal Title: J Clin Oncol Volume: 31 Issue: 29 Pages: 3704-3710
  • DOI: 10.1200/jco.2013.50.3789
  • Peer Reviewed
• [Presentation] Gene expression profiling of Japanese gastric cancer patinets using Asian Cancer Research Group classification. (2016)
  • Author(s): Masanori Terashima, Rie Makuuchi, Masanori Tokunaga, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Makoto Hikage, Keiichi Hatakeyama, Keiichi Oshima, Shunpei Ohnami, Kennichi Urakami, Masatoshi Kusuhara, Ken Yamaguchi
  • Organizer: 2016 Gastrointestinal Cancers Symposium
  • Place of Presentation: San Francisco
  • Year and Date: 2016-01-21
  • Int'l Joint Research
• [Presentation] Whole exome sequencing and gene expression profiling of neuroendocrine carcinoma in the stomach. (2016)
  • Author(s): Rie Makuuchi, Masanori Terashima, Masanori Tokunaga, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Keiichi Hatakeyama, Masatoshi Kusuhara, Ken Yamaguchi, Keiichi Oshima, Kennichi Urakami, Makoto Hikage
  • Organizer: 2016 Gastrointestinal Cancers Symposium
  • Place of Presentation: San Francisco
  • Year and Date: 2016-01-21
  • Int'l Joint Research
• [Presentation] 分子プロファイルに基づく胃癌の分類 (2015)
  • Author(s): 幕内梨恵、寺島雅典、本田晋策、高木航、辰林太一、日景允、徳永正則、谷澤豊、坂東悦郎、川村泰一、畠山慶一、大島啓一、浦上研一、楠原正敏、山口建
  • Organizer: 第53回日本癌治療学会
  • Place of Presentation: 京都
  • Year and Date: 2015-10-29
• [Presentation] Conversion Surgery after Chemotherapy for Unresectable Advanced Gastric Cancer - What is the Evidence (2015)
  • Author(s): Terashima M
  • Organizer: Singapore Gastric Cancer Consortium 8th Annual Scientific Meeting
  • Place of Presentation: Singapore
  • Year and Date: 2015-07-22
  • Int'l Joint Research / Invited
• [Presentation] 食道癌の進行が代謝プロファイルに与える影響―CE TOFMS を用いたメタボローム解 析の結果から― (2015)
  • Author(s): 徳永正則、小澤壯治、紙健次郎、宮地勇人、數野暁人、山崎康、小熊潤也、二宮大和、大橋由明、藤森玉輝、星綾、楠原正俊、寺島雅典
  • Organizer: 第115回日本外科学会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-04-16
• [Presentation] Survivin expression in circulating tumor cells of patients with gastric cancer (2014)
  • Author(s): Terashima M, Hatakeyama K, Yamakawa Y, Sugisawa N, Miki Y, Makuuchi R, Goto H, Tokunaga M, Tanizawa Y, Bando E, Kawamura T, Oshima K, Mochizuki T
  • Organizer: Gastrointestinal Cancer Symposium 2014
  • Place of Presentation: San Francisco, USA
• [Presentation] Identification of novel protein isoforms in secretome using combined analysis of microarray and mass spectrometry (2013)
  • Author(s): Hatakeyama K, Ohshima K, Wakabayashi-Nakao K, Tanizawa Y, Terashima M, Yamaguchi K, Mochizuki T
  • Organizer: 第75会日本癌学会
  • Place of Presentation: 横浜
• [Book] 胃がん外来化学療法へのアプローチ (2016)
  • Author(s): 寺島雅典
  • Total Pages: 123
  • Publisher: 医薬ジャーナル社
• [Book] 胃切除後障害診療ハンドブック (2015)
  • Author(s): 寺島雅典
  • Total Pages: 169
  • Publisher: 南江堂
• [Book] EBMがん化学療法・分子標的治療法 (2015)
  • Author(s): 寺島雅典
  • Total Pages: 713
  • Publisher: 中外医学社
• [Book] 胃外科のすべて (2014)
  • Author(s): 寺島雅典
  • Total Pages: 351
  • Publisher: メジカルビュー社