Verification of diagnostic biomarker candidates for biliary and pancreatic carcinoma by SRM MS-based Multiple Assay

2010 Fiscal Year Final Research Report

• Project/Area Number: 19689028
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Tohoku University
• Principal Investigator: ONOGAWA Tohru 東北大学, 病院, 助教 (50431557)
• Project Period (FY): 2007 – 2010
• Keywords: 薬物輸送体 / 抗癌剤感受性 / プロテオミクス / バイオマーカー / 質量分析

Research Abstract

Cholangiocarcinoma (CC) is usually diagnosed in advanced stage and associated with a dismal prognosis. A proteomic analysis may help identify novel biomarkers for the eraly detection, prevention and treatment of CC. The purpose of this study was to identify proteins differentially overexpressed in CC and to validate these proteins as potential biomarkers. We conducted a retrospective global proteomic sthdy of formalin-fixed parafiin-embedded (FEPE) tissues by shotgun LC-MS/MS. We identified abouto 2000 proteins, and statistical comparison showed that 160 proteins were overexpressed in CC compared to noncancerous bile duct. We applied a targeted proteomics approach based on selected reaction monitoring (SRM) to quantify a subset of these proteins. SRM analysis suggested that some proteins would be useful as potential biomarkers. Expression of these proteins was cinfirmed by immunohistochemistry. Further validation using a large-scale sample set of FFPE tissues is now under way.

Research Products

• [Journal Article] Computed tomography reflected endocrine function of the pancreas (2011)
  • Author(s): Sakata N, Egawa S, Rikiyama T, Yoshimatsu G, Masuda K, Ohtsuka H, Ottomo S, Nakagawa K, Hayashi H, Morikawa T, Onogawa T, Yamamoto K, Yoshida H, Akada M, Motoi F, Naitoh T, Katayose Y, Unno M
  • Journal Title: J Gastrointest Surg. Volume: 15(3) Pages: 535-32
  • Peer Reviewed
• [Journal Article] Paclitaxel as second-line chemotherapy in patients with gemcitabine-refractory pancreatic cancer: a retrospective study (2011)
  • Author(s): Maeda S, Motoi F, Onogawa T, Morikawa T, Shigeru O, Sakata N, Takadate T, Naitoh T, Rikiyama T, Katayose Y, Egawa S, Unno M
  • Journal Title: Int J Clin Oncol. Volume: (in Press)
  • Peer Reviewed
• [Journal Article] The HMG-CaA reductase inhibitor prevastatin stimulates insulin secretion through organic anion transporter polypeptides (2010)
  • Author(s): Abe M, Toyohara T, Ishii A, Suzuki T, Noguchi N, Akiyama Y, Shiwaku HO, Nakagomi-Hagugara R, Zheng G, Shibata E, Souma T, Shindo T, Shima H, Takeuchi Y, Mishima E, Tanemoto M, Terasaki T, Onogawa T, Unno M, Ito S, Takasawa S, Abe T
  • Journal Title: Drug Metab Pharmacokinet Volume: 25(3) Pages: 274-82
  • Peer Reviewed
• [Journal Article] Assessment of Frey procedures: Japanese experience (2010)
  • Author(s): Egawa S, Motoi F, Sakata N, Kitamura Y, Nakagawa K, Ohtsuka H, Hayashi H, Morikawa T, Omura N, Ottomo S, Yoshida H, Onogawa T, Yamamoto K, Akada M, Rikiyama T, Katayose Y, Matsuno S, Unno M
  • Journal Title: J Hepatoviliary Pancreat Sci Volume: 17(6) Pages: 745-41
  • Peer Reviewed
• [Journal Article] Overexpression of adenovirus-mediated p27kip1 lacking the Jab1-binding region enhances cytotoxicity and inhibits xenografted human cholangiocarcinoma growth (2009)
  • Author(s): Shiraso S, Katayose Y, Yamamoto K, Muzuma M, Yabuuchi S, Oda A, Rikiyama T, Onogawa T, Yoshida H, Hayashi H, Ohtsuka H, Motoi F, Egawa S, Kato J, Unno M
  • Journal Title: Anticancer Res. Volume: 29(6) Pages: 2015-24
  • Peer Reviewed
• [Journal Article] Clock gene mouse period2 overexpression inhibits growth ot fuman pancreatic cancer cells and has synergistic effect with cisplatin (2009)
  • Author(s): Oda A, Katayose Y, Yabuuchi S, Yamamoto K, Mizuma M, Shirasou S, Onogawa T, Ohtsuka H, Yoshida H, Hayashi H, Rikiyama T, Kim H, Choe Y, Kim K, Son H, Motoi F, Egawa S, Unno M
  • Journal Title: Anticancer Res. Volume: 29(4) Pages: 1201-9
  • Peer Reviewed
• [Journal Article] ZD1839 (IRESSA) stabilizes p27^<Kip1> and enhances radiosensitivity in cholangiocarcinoma cell lines (2009)
  • Author(s): Yabuuchi S, Katayoshi Y, Oda A, Mizuma M, Shirasou S, Sasaki T, Yamamoto K, Oikawa M, Rikiyama T, Onogawa T, Yoshida H, Ohtsuka H, Motoi F, Egawa S, Unno M
  • Journal Title: Anticancer Res. Volume: 29(4) Pages: 1169-80
  • Peer Reviewed
• [Journal Article] Up-regulated p27Kip1 reduces matrix metalloproteinase-9 and inhibits invasion of human breast cancer cells (2008)
  • Author(s): Mizuma M, Katayose Y, Yamamoto K, Shirano S, Sasaki T, Yabuuchi S, Oda A, Masuda K, Rikiyama T, Yabuuchi S, Oda A, Masuda K, Rikiyama T, Onogawa T, Ohtsuka H, Motoi F, Egawa S, Unno M
  • Journal Title: Anticancer Res. Volume: 28(5A) Pages: 2669-77
  • Peer Reviewed
• [Journal Article] Advanced bile duct carcinoma in a 15-year-old patient with pancreaticobiliary maljunction and congenital biliary cystic disease (2008)
  • Author(s): Nakamura H, Katayose Y, Rikiyama T, Onogawa T, Yamamoto K, Yoshida H, Hayashi H, Ohtsuka H, Hayashi Y, Egawa S, Unno M
  • Journal Title: J Hepatobiliary Pancreat Surg Volume: 15(5) Pages: 554-9
  • Peer Reviewed
• [Journal Article] Bile acids repress E-cadherin through the induction of Snail and increase cancer invasiveness in human hepatobiliary carcinoma (2008)
  • Author(s): Fukase K, Ohtsuka H, Onogawa T, Oshio H, Ii T, Mutoh M, Katayose Y, Rikiyama T, Oikawa M, Motoi F, Egawa S, Abe T, Unno M
  • Journal Title: Cancer Sci. Volume: 99(9) Pages: 1785-92
  • Peer Reviewed
• [Journal Article] Peroxisome proliferator -activated receptor alpha activates cyclooxygenase-2 gene transcription through bile acid transport in human colorectal cancer cell lines (2008)
  • Author(s): Oshio H, Abe T, Onogawa T, Ohtsuka H, Sato T, Ii T, Fukase K, Muto M, Katayose Y, Oikawa M, Rikiyama T, Egawa S, Unno M
  • Journal Title: J Gastroenterol Volume: 43(7) Pages: 538-49
  • Peer Reviewed
• [Journal Article] Adenovirus expressing mutant p27kip1 enhanced apoptosis and inhibited the growth of xenografted human breast cancer (2007)
  • Author(s): Sakai T, Katayose Y, Yamamoto K, Mizuma M, Shiraso S, Yabuuchi S, Oda A, Rikiyama T, Oikawa M, Onogawa T, Suzuki M, Lee CT, Unno M
  • Journal Title: Surg Today Volume: 37(12) Pages: 1073-82
  • Peer Reviewed
• [Journal Article] Human liver-specific organic anion transporter-2 is a potent prognostic factor for human breast carcinoma (2007)
  • Author(s): Onogawa T, Muto M, Suzuki T, Ishida T, Rikiyama T, Katayose Y, Ohuchi N, Sasano H, Abe T, Unno M
  • Journal Title: Cancer Sci. Volume: 98(10) Pages: 1570-6
  • Peer Reviewed
• [Journal Article] Expression of organic cation transporter SLC22A16 in human epithelial ovarian cancer: a possible role of the adriamycin importer (2007)
  • Author(s): Ota K, Ito K, Akahira H, Sato N, Onogawa T, Moriya T, Unno M, Abe T, Niikura H, Takano T, Yaegashi N
  • Journal Title: Int J Gynecol Pathol Volume: 26(3) Pages: 334-40
  • Peer Reviewed
• [Presentation] ホルマリン固定パラフィン包理(FFPE)組織切片の臨床プロテオーム解析における基礎パラメータの検討 (2010)
  • Author(s): 小野川徹ら(15名中1番目)
  • Organizer: 日本ヒトプロテオーム機構第8回大会・第6回日本臨床プロテオーム研究会連合大会
  • Place of Presentation: 浦安
  • Year and Date: 2010-07-26
• [Presentation] 胆道癌FFPE組織を用いた網羅的プロテオーム解析による新規バイオマーカーの探索と検証 (2010)
  • Author(s): 前田晋平, 小野川徹ら
  • Organizer: 日本ヒトプロテオーム機構第8回大会・第6回日本臨床プロテオーム研究会連合大会
  • Place of Presentation: 浦安
  • Year and Date: 2010-07-26
• [Presentation] FFPEを用いた網羅的プロテオーム解析による膵癌新規予後予測マーカーの探索 (2010)
  • Author(s): 高舘達之, 小野川徹ら
  • Organizer: 日本ヒトプロテオーム機構第8回大会・第6回日本臨床プロテオーム研究会連合大会
  • Place of Presentation: 浦安
  • Year and Date: 2010-07-26
• [Presentation] Discoverty of Prognostic Factor using Proteomic Analysis with Formalin-Fixed Paraffin-Embedded Tissues of Pancreatic Cancer (2010)
  • Author(s): Takadate T, Onogawa T, et al.
  • Organizer: the Joint Meeting of the International Association of Pancreatology and the Japan Pancreas Society
  • Place of Presentation: Fukuoka
  • Year and Date: 2010-07-11
• [Presentation] 病院保管のホルマリン固定組織からプロテオーム解析はどこまでできるか? (2010)
  • Author(s): 小野川徹ら(21名中1番目)
  • Organizer: 第22回日本肝胆膵外科学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2010-06-28
• [Presentation] 胆道癌ホルマリン固定パラフィン包理切片からのディスカバリープロテオミクス (2009)
  • Author(s): 小野川徹ら(21名中1番目)
  • Organizer: 日本ヒトプロテオーム機構第7回大会
  • Place of Presentation: 東京
  • Year and Date: 2009-07-27
• [Presentation] 胆道癌ホルマリン固定パラフィン包理組織からのディスカバリープロテオミクス (2009)
  • Author(s): 小野川徹ら(21名中1番目)
  • Organizer: 第5回日本臨床プロテオーム研究会
  • Place of Presentation: 東京
  • Year and Date: 2009-05-09
• [Presentation] 新規乳癌独立予後規定因子LST-2/SLC01B3の癌細胞特異的発現とその主要生物学的意義 (2008)
  • Author(s): 小野川徹ら(8名中1番目)
  • Organizer: 第3回トランスポーター研究会年会
  • Place of Presentation: 京都
  • Year and Date: 2008-06-07
• [Presentation] 検体微量ペプチド試料からの薬物輸送体及び代謝酵素蛋白群の網羅的同時絶対定量解析と抗癌剤感受性予測 (2008)
  • Author(s): 小野川徹ら(18名中1番目)
  • Organizer: 第108回日本外科学会定期学術集会
  • Place of Presentation: 長崎
  • Year and Date: 2008-05-15
• [Book] Deseases of the Pancreas -Current Surgical Therapy-(共著書) (Beger HG, Matsuno S, Cameron JL Eds.), Section 10 : Congenital Anomalies of the Pancreas, Chapter 82 : Biliopancreatic Maljunction: Classification, Diagnosis, and Treatment (2008)
  • Author(s): Onogawa T, Rikiyama T, Unno M, Matsuno S.
  • Total Pages: 895-904
  • Publisher: Springer-Verlag Berlin Heidelberg
• [Patent(Industrial Property Rights)] 胆道がん診断用新規バイオマーカー群 (2011)
  • Inventor(s): 小野川徹, 海野倫明, 前田晋平
  • Industrial Property Rights Holder: 国立大学法人東北大学
  • Industrial Property Number: 特許願, 特願2011-107624
  • Filing Date: 2011-05-12