Biomarker searches and clinical applications of gastrointestinal and hepatobiliary cancers by multidisciplinary approaches

• Project/Area Number: 22390114
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Chiba University
• Principal Investigator: NOMURA Fumio 千葉大学, 大学院・医学研究院, 教授 (80164739)
• Co-Investigator(Renkei-kenkyūsha): TOMONNAGA Takeshi 独立行政法人医薬基盤研究所, 基盤的研究部プロテオームリサーチプロジェクト, プロジェクトリーダー (80227644) ; KODERA Yoshio 北里大学, 理学部, 准教授 (60265733) ; MATSUSHITA Kazuyuki 千葉大学, 大学院・医学研究院, 准教授 (90344994) ; SOGAWA Kazuyuki 麻布大学, 生命・環境科学部, 講師 (50436440)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2011: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2010: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
• Keywords: 蛋白質 / プロテオーム / 癌 / 臨床 / 検査医学 / ペプチドマーカー

Research Abstract

Novel biomarker for excessive drinking was determined by serum deep proteome analyses. In addition to expression proteomics, antibody against proteins overexpressed in cancer tissues were explored. Serum anti-Ku86 was found to be a potential early diagnostic marker for hepatocellular carcinoma. Gingival crevicular fluid (GCF) was analyzed as a typical example of proximal fluids to search for biomarkers of periodontal diseases.

Research Products

• [Journal Article] Combined Proteomic Analysis of Liver Tissue and Serum in Chronically Alcohol-Fed Rats (2013)
  • Author(s): Yamada M, Satoh M, Seimiya M, Sogawa K, Itoga S, Tomonnaga T, Nomura F
  • Journal Title: Alcohol Clin Exp Res Volume: 37 Suppl 1
  • Peer Reviewed
• [Journal Article] Plectin promotes migration and invasion of cancer cells and is a novel prognostic marker for head and neck squamous cell carcinoma (2012)
  • Author(s): Katada K, Tomonnaga T, Satoh M,Matsushita K, Tonoike Y, Kodera Y, Hanazawa T, Nomura F, Okamoto Y
  • Journal Title: J Proteomics Volume: 75(6) Pages: 1803-15
  • Peer Reviewed
• [Journal Article] Proteomic analysis of gingival crevicular fluid for discovery of novel periodontal diseasemarkers (2012)
  • Author(s): Tsuchida S, Satoh M, Umemura H, Sogawa K, Kawashima Y, Kado S, Sawai S, Nishimura M, Kodera Y, Matsushita K, Nomura F
  • Journal Title: Proteomics Volume: 12(13) Pages: 2190-202
  • Peer Reviewed
• [Journal Article] Identification of a Novel Biomarker for Biliary Tract Cancer Using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (2012)
  • Author(s): Kikkawa S, Sogawa K, Satoh M,図 4Umemura H, Kodera Y, Matsushita K, Tomonnaga T, Miyazaki, Yokosuka O, Nomura F
  • Journal Title: Int J Proteomics Pages: 108609-108609
  • Peer Reviewed
• [Journal Article] Prohibitin in squamous cell carcinoma of the lung: its expression and possible clinical significance (2012)
  • Author(s): Guo F, Hiroshima K, Wu D, Satoh M, Abulazi M, Yoshino I, Tomonnaga T, Nomura F, Nakatani Y
  • Journal Title: Hum Pathol Volume: 43(8) Pages: 1282-8
  • Peer Reviewed
• [Journal Article] The application of a three-step serum proteome analysis for the discovery and identification of novel biomarkers of hepatocellular carcinoma (2012)
  • Author(s): Kimura A, Sogawa K, Satoh M, Kodera Y, Yokosuka O, Tomonnaga T, Nomura F
  • Journal Title: Int J Proteomics Pages: 623190-623190
  • Peer Reviewed
• [Journal Article] Plectin promotes migration and invasion of cancer cells and is a novel prognostic marker for head and neck squamous cell carcinoma. (2012)
  • Author(s): Katada K
  • Journal Title: J Proteomics. Volume: 75(6) Pages: 1803-15
  • Peer Reviewed
• [Journal Article] Serum anti-Ku86 is a potential biomarker for early detection of hepatitis C virus-related hepatocellular carcinoma. (2012)
  • Author(s): Nomura F
  • Journal Title: Biochem Biophys Res Commun. Volume: 421(4) Pages: 837-43
  • Peer Reviewed
• [Journal Article] Proteomic analysis of gingival crevicular fluid for discovery of novel periodontal disease markers. (2012)
  • Author(s): Tsuchida S
  • Journal Title: Proteomics. Volume: 12(13) Issue: 13 Pages: 2190-202
  • DOI: 10.1002/pmic.201100655
  • Peer Reviewed
• [Journal Article] The application of a three-step proteomeanalysis for identification of new biomarkers of pancreatic cancer (2011)
  • Author(s): Abulaizi M, Tomonnaga T, Satoh M, Sogawa K, Matsushita K, Kodera Y, Obul J, Takano S, Yoshitomi H, Miyazaki M, Nomura F
  • Journal Title: Int J Proteomics Volume: 2011 Pages: 628787-628787
  • Peer Reviewed
• [Journal Article] Serum Level of Fibrinogen Aα Chain Fragment Increases in Chronic Thromboembolic Pulmonary Hypertension (2011)
  • Author(s): Yano T, Sogawa K, Umemura H, Sakao S, Kasahara Y, Tanabe N, Kodera Y, Takiguchi Y, Tatsumi K, Nomura F
  • Journal Title: Circ J Volume: 75(11) Pages: 2675-82
  • NAID: 10030032528
  • Peer Reviewed
• [Journal Article] Identification of vitronectin as a novel serum marker for early breast cancer detection using a new proteomic approach (2011)
  • Author(s): Kadowaki M, Sangai T, Nagashima T, Sakakibara M, Yoshitomi H, Takano S,Sogawa K, Umemura H, Fushimi K, Nakatani Y, Nomura F, Miyazaki M
  • Journal Title: J Cancer Res Clin Oncol Volume: 137(7) Pages: 1105-15
  • Peer Reviewed
• [Journal Article] The measurement of a fibrinogen α C-chain 5.9kDa fragment (FIC 5.9) using MALDI-TOF MS and a stable isotope-labeled peptide standard dilution (2011)
  • Author(s): Sogawa K, Kodera Y, Noda K, Ishizuka Y, Yamada M, Umemura H, Maruyama K, Tomonnaga T, Yokosuka O, Nomura F
  • Journal Title: Clin Chim Acta Volume: 412(11-12) Pages: 1094-9
  • Peer Reviewed
• [Journal Article] Identification of a high molecular weight kininogen fragment as a marker for early gastric cancer by serum proteome analysis (2011)
  • Author(s): Umemura H, Togawa A, Sogawa K, Satoh M, Mogushi K, Nishimura M, Matsushita K, Tanaka H, Takizawa H, Kodera Y, Nomura F
  • Journal Title: J Gastroenterol Volume: 46(5) Pages: 577-85
  • NAID: 10029028943
  • Peer Reviewed
• [Journal Article] Development of a sandwich ELISA for the 5.9-kDa fibrinogen alpha C chain fragment detected by serum proteome analysis (2011)
  • Author(s): Noda K, Sogawa K, Kikuchi W, Kiyokawa I, Miura T, Kojima R, Katayama K, Kodera Y, Nomura F
  • Journal Title: Proteomics Clin Appl Volume: 5(3-4) Pages: 141-6
  • Peer Reviewed
• [Journal Article] Increased Serum Levels of Pigment Epithelium-Derived Factor by Excessive Alcohol Consumption-Detection and Identification by a Three-Step Serum Proteome Analysis (2011)
  • Author(s): Sogawa K, Kodera Y, Satoh M, Kawashima Y, Umemura H, Maruyama K, Takizawa H, Yokosuka O, Nomura F
  • Journal Title: Alcohol Clin Exp Res Volume: 35(2) Pages: 211-7
  • Peer Reviewed
• [Journal Article] Identification of Subtilase cytotoxin (SubAB) receptors whose signaling, in association with SubAB-induced BiP cleavage, is responsible for apoptosis in HeLa cells (2011)
  • Author(s): Yahiro K, Satoh M, Morinaga N, Tsutsuki H, Ogura K, Nagasawa S, Nomura F, Moss J, Noda M
  • Journal Title: Infect Immun Volume: 79(2) Pages: 617-27
  • Peer Reviewed
• [Journal Article] The application of a three-step proteome analysis for identification of new biomarkers of pancreatic cancer (2011)
  • Author(s): Abulaizi M, Tomonaga T, Satoh M, Sogawa K, Matsushita K, Kodera Y, Obul J, Takano S, Yoshitomi H, Miyazaki M, Nomura F
  • Journal Title: Int J Proteomics Volume: 628787
  • Peer Reviewed
• [Journal Article] Identification of Subtilase cytotosin (SubAB) receptors whose signaling, in association with Subr1B-induced BiP cleavage, is responsible for apoptosis in HeLa cells. (2011)
  • Author(s): Yahiro K
  • Journal Title: Infect Immun. Volume: 79 Pages: 617-627
  • Peer Reviewed
• [Journal Article] Effects of humidity on the dried-droplet sample preparation for MALDI-TOF MS peptide profiling (2010)
  • Author(s): Umemura H, Kodera Y, Nomura F
  • Journal Title: Clin Chim Acta Volume: 411(23-24) Pages: 2109-11
  • Peer Reviewed
• [Journal Article] Reduction of novel circulating long-chain fatty acids in colorectal cancer patients is independent of tumor burden and correlates with age (2010)
  • Author(s): Ritchie SA, Heath D, Yamazaki Y, Grimmalt B, Kavianpour A, Krenitsky K, Elshoni H, Takemasa I, Miyake M, Sekimoto M, Monden M, Tomonnaga T, Matsubara H, Sogawa K, Matsushita K, Nomura F, Goodenowe DB
  • Journal Title: BMC Gastroenterol Volume: 10 Pages: 140-140
  • Peer Reviewed
• [Journal Article] Increased circulating cell signalling phosphoproteins in sera are useful for the detection of pancreatic cancer (2010)
  • Author(s): Takano S, Sogawa K, Yoshitomi H, Shida T, Mogushi K, Kimura F, Shimizu H, Yoshidome H, Ohtsuka M,Kato A, Ishihara T, Tanaka H, Yokosuka O, Nomura F, Miyazaki M
  • Journal Title: Br J Cancer Volume: 103(2) Pages: 223-31
  • Peer Reviewed
• [Journal Article] High-yield peptide-extraction method for the discovery of subnanomolar biomarkers from small serum samples (2010)
  • Author(s): Kawashima Y, Fukutomi T, Tomonnaga T, Takahashi H, Nomura F, Maeda T, Kodera Y
  • Journal Title: J Proteome Res Volume: 9(4) Pages: 1694-705
  • Peer Reviewed
• [Journal Article] High-yield peptide-extraction method for the discovery of subnanomolar biomarkers from small serum samples. (2010)
  • Author(s): Kawashima Y
  • Journal Title: J Proteome Res. Volume: 94 Pages: 1694-1705
  • Peer Reviewed
• [Journal Article] Increased circulating cell signalling phosphoproteins in sera are useful for the detection of pancreatic cancer. (2010)
  • Author(s): Takano S
  • Journal Title: Br J Cancer Volume: 103 Pages: 223-231
  • Peer Reviewed
• [Journal Article] Reduction of novel circulating long chain fatty acids in colorectal cancer patients is independent of tumor burden and correlates with age. (2010)
  • Author(s): Ritchie SA.
  • Journal Title: BMC Gastroenterol. Volume: 10 Pages: 140-140
  • Peer Reviewed
• [Journal Article] Effects of humidity on the dried droplet sample preparation for MALDI-TOF MS peptide profiling. (2010)
  • Author(s): Umemura H
  • Journal Title: Clin Chim Acta. Volume: 411 Pages: 2109-2111
  • Peer Reviewed
• [Presentation] 歯肉溝滲出液のプロテオーム解析による歯周疾患マーカーの探索 (2012)
  • Author(s): 土田祥央、佐藤守、曽川一幸、川島祐介、荷堂清香、澤井摂、西村基、小寺義男、松下一之、野村文夫
  • Organizer: 第19回日本遺伝子診療学会大会
  • Place of Presentation: 三井ガーデンホテル千葉
  • Year and Date: 2012-07-28
• [Presentation] Diagnostic Value of Serum anti-Ku86 Levels in the Early Detection of Hepatitis C Virus-related Hepatocellular Carcinoma. (2012)
  • Author(s): Fumio Nomura
  • Organizer: AASLD (American Association of the Study of Liver Diseases)
  • Place of Presentation: Boston, USA
• [Presentation] DIAGNOSTIC VALUE OF SERUM ANTI-KU86 LEVELS IN THE EARLY DETECTION OF HEPATITIS C VIRUS-RELATED HEPATOCELLULAR CARCINOMA (2011)
  • Author(s): Nomura F, Sogawa K, Noda K, Seimiya M, Matsushita K, Tomonnaga T, Yokosuka O
  • Organizer: The 62th Annual Meeting of the American Association for the Study ofLiver Diseases: The Liver Meeting2011
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-11-05
• [Presentation] DIAGNOSTIC VALUE OF SERUM ANTI-KU86 LEVELS IN THE EARLY DETECTION OF HEPATITIS C VIRUS-RELATED HEPATOCELLULAR CARCINOMA (2011)
  • Author(s): Nomura F, Sogawa K, Noda K, Seimiya M, Matsushita K, Tomonaga T, Yokosuka O
  • Organizer: The 62th Annual Meeting of the American Association for the Study of Liver Diseases : The Liver Meeting 2011
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-11-05
• [Presentation] 卵巣癌に特異的な代謝プロファイルの同定 (2011)
  • Author(s): 三橋暁、パストゥラルエロディ、山崎泰代、リッティーショーン、曽川一幸、生水真紀夫、野村文夫、グッデナゥダイアン
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-04
• [Presentation] SERUM FIC5.9 LEVELSAS A PROMISING BIOMARKER FOR DETECTING LIVER PATHOLOGIES (2011)
  • Author(s): Noda K, Kikuti W, Kiyokawa I, Miura T, Kojima R, Katayama K, Sogawa K, Nomura F
  • Organizer: HUPO 10^<th> Annual World Congress
  • Place of Presentation: Geneva, Swiss
  • Year and Date: 2011-09-05
• [Presentation] SERUM FIC5.9 LEVELS AS A PROMISING BIOMARKER FOR DETECTING LIVER PATHOLOGIES (2011)
  • Author(s): Noda K, Kikuti W, Kiyokawa I, Miura T, Kojima R, Katayama K, Sogawa K, Nomura F
  • Organizer: HUPO 10th Annual World Congress
  • Place of Presentation: Geneva, Swiss
  • Year and Date: 2011-09-05
• [Presentation] ジェムシタビン耐性ヒト膵癌細胞株のプロテオーム解析 (2011)
  • Author(s): 佐藤守、高野重紹、石橋真澄、吉富秀幸、西村基、曽川一幸、松下一之、賀川真吾、荷堂清香、宮崎勝、野村文夫
  • Organizer: 第9回日本人プロテオーム機構大会
  • Place of Presentation: 朱鷺メッセ(新潟)
  • Year and Date: 2011-07-28
• [Presentation] ジェムシタビン耐性ヒト膵癌細胞株のプロテオーム解析 (2011)
  • Author(s): 佐藤守、高野重紹、石橋真澄、吉富秀幸、西村基、曽川一幸、松下一之、賀川真吾、荷堂清香、宮崎勝、野村文夫
  • Organizer: 第9回日本ヒトプロテオーム機構大会
  • Place of Presentation: 朱鷺メッセ(新潟)
  • Year and Date: 2011-07-28
• [Presentation] プロテオーム解析による肝疾患の新たなバイオマーカーの探索と臨床応用 (2010)
  • Author(s): 野村文夫
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] プロテオーム解析による肝疾患の新たなバイオマーカーの探索と臨床応用 (2010)
  • Author(s): 野村文夫
  • Organizer: BMB 2010(日本生化学会・日本分子生物学会)ワークショップ
  • Place of Presentation: 神戸市
  • Year and Date: 2010-12-07
• [Presentation] Comprehensive proteomeanalysis in search for biomarkers of hepatocellular carcinoma and its high-risk group (2010)
  • Author(s): 野村文夫
  • Organizer: 第69回日本癌学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] Comprehensive proteome analysis in search for biomarkers of hepatocellular carcinoma and its high risk group (2010)
  • Author(s): 野村文夫
  • Organizer: 第69回日本癌学会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-09-24
• [Presentation] プロテオーム解析により見出 された肝疾患の新しいバイオマーカー (2010)
  • Author(s): 野村文夫
  • Organizer: 第10回日本蛋白質科学会
  • Place of Presentation: 札幌
  • Year and Date: 2010-06-08
• [Presentation] プロテオーム解析により見出された肝疾患の新しいバイオマーカー (2010)
  • Author(s): 野村文夫
  • Organizer: 第10回日本蛋白質科学会
  • Place of Presentation: 札幌市
  • Year and Date: 2010-06-08
• [Presentation] 歯肉溝滲出液のプロテオーム解析による歯周疾患マーカーの探索.
  • Author(s): 土田祥央
  • Organizer: 第19回日本遺伝子診療学会大会
  • Place of Presentation: 千葉