Identification of novel biomarkers for pancreato-biliary cancer by comprehensive protein profiling analysis

• Project/Area Number: 26293299
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: International University of Health and Welfare (2016); Chiba University (2014-2015)
• Principal Investigator: Miyazaki Masaru 国際医療福祉大学, 大学病院, 教授 (70166156)
• Co-Investigator(Kenkyū-buntansha): 高野 重紹 千葉大学, 医学部附属病院, 助教 (20436380) ; 久保木 知 千葉大学, 医学部附属病院, 助教 (50571410) ; 吉富 秀幸 千葉大学, 医学部附属病院, 講師 (60375631) ; 加藤 厚 千葉大学, 医学(系)研究科(研究院), 講師 (70344984) ; 清水 宏明 千葉大学, 医学(系)研究科(研究院), 准教授 (80272318) ; 大塚 将之 千葉大学, 医学(系)研究科(研究院), 講師 (90334185) ; 賀川 真吾 千葉大学, 医学部附属病院, 助教 (90507302)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000)
• Keywords: 癌 / 外科 / プロテオーム

Outline of Final Research Achievements

We aimed to elucidate the key molecules involved in pancreatic ductal adenocarcinoma (PDAC) progression using proteomics approaches. First, we performed two-dimensional electrophoresis to identify the proteins overexpressed in PDAC tissues. Cofilin-1 were identified and verified as a candidate protein commonly upregulated in PDAC tissues. In immunohistochemistry, samples were divided into two groups based on the level of cofilin-1 expression, the High expression group showed significantly higher incidence of hematogenous dissemination in relapse forms of patients than did the Low expression group. After we established a detection system for immune-complex (IC) of cofilin-1 in sera, we observed that cofilin-1 IC levels in PDAC patients were significantly higher than those in healthy volunteers and patients with pancreatitis. Notably, those levels showed a stepwise increase during PDAC progression. These results suggest that cofilin-1 IC in sera is a potential serum biomarker for PDAC.

Research Products

• [Journal Article] Immune-complex level of cofilin-1 in sera is associated with cancer progression and poor prognosis in pancreatic cancer. (2017)
  • Author(s): Satoh M, Takano S, Sogawa K, Noda K, Yoshitomi H, Ishibashi M, Mogushi K, Takizawa H, Otsuka M, Shimizu H, Miyazaki M, Nomura F.
  • Journal Title: Cancer Sci. Volume: 印刷中 Issue: 4 Pages: 795-803
  • DOI: 10.1111/cas.13181
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Portal vein thrombosis after reconstruction in 270 consecutive patients with portal vein resections in hepatopancreatobiliary (HPB) surgery. (2017)
  • Author(s): Miyazaki M, Shimizu H, Ohtuka M, Kato A, Yoshitomi H, Furukawa K, Takayashiki T, Kuboki S, Takano S, Suzuki D, Higashihara T.
  • Journal Title: Am J Surg. Volume: 印刷中 Issue: 1 Pages: 74-79
  • DOI: 10.1016/j.amjsurg.2016.12.008
  • Peer Reviewed
• [Journal Article] Combined hepatic arterial resection in pancreatic resections for locally advanced pancreatic cancer. (2017)
  • Author(s): Miyazaki M, Yoshitomi H, Takano S, Shimizu H, Kato A, Yoshidome H, Furukawa K, Takayashiki T, Kuboki S, Suzuki D, Sakai N, Ohtuka M.
  • Journal Title: Langenbecks Arch Surg. Volume: 402 Issue: 3 Pages: 447-456
  • DOI: 10.1007/s00423-017-1578-5
  • Peer Reviewed
• [Journal Article] Identification of a novel serum biomarker for pancreatic cancer, C4b-binding protein α-chain (C4BPA) by quantitative proteomic analysis using tandem mass tags. (2016)
  • Author(s): Sogawa K, Takano S, Iida F, Satoh M, Tsuchida S, Kawashima Y, Yoshitomi H, Sanda A, Kodera Y, Takizawa H, Mikata R, Ohtsuka M, Shimizu H, Miyazaki M, Yokosuka O, Nomura F.
  • Journal Title: Br J Cancer. Volume: 115 Issue: 8 Pages: 949-956
  • DOI: 10.1038/bjc.2016.295
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Annexin II induces gemcitabine resistance via Akt/mTOR signaling pathway and predicts rapid recurrence after surgery in pancreatic cancer. (2016)
  • Author(s): S. Takano, H. Yoshitomi, S. Kagawa, H. Shimizu, M. Ohtsuka, A. Kato, K. Furukawa, T. Takayashiki, S. Kuboki, D. Suzuki, N. Sakai, H. Nojima and M. Miyazaki.
  • Organizer: 第47回日本膵臓学会大会、第20回国際膵臓学会、第6回アジアオセアニア膵臓学会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-08-04
  • Int'l Joint Research
• [Presentation] Annexin II発現における膵癌バイオマーカーの臨床学的意義 (2016)
  • Author(s): 高野重紹、吉富秀幸、賀川真吾、清水宏明、大塚将之、加藤 厚、古川勝規、高屋敷 吏、久保木 知、鈴木大亮、酒井 望、野島広之、宮崎 勝
  • Organizer: 第116回日本外科学会定期学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2016-04-14
• [Presentation] Identification of Cofilin as a useful biomarker in pancreatic cancer progression. (2015)
  • Author(s): Shigetsugu Takano, Mamoru Satoh, Kazuyuki Sogawa, Hideyuki Yoshitomi, Hiroaki Shimizu, Masayuki Ohtsuka, Atsushi Kato, Satoshi Kuboki, Shingo Kagawa, Kazuyuki Matsushita, Fumio Nomura and Masaru Miyazaki
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] 自己免疫複合体測定法による膵癌バイオマーカーの臨床学的意義 (2015)
  • Author(s): Shingo Kagawa, Shigetsugu Takano, Mamoru Satoh, Kazuyuki Sogawa, Hideyuki Yoshitomi, Hiroaki Shimizu, Masayuki Ohtsuka, Atsushi Kato, Katsunori Furukawa, Tsukasa Takayashiki, Satoshi Kuboki, Daiki Okamura, Daisuke Suzuki, Nozomu Sakai, Fumio Nomura, Masaru Miyazaki
  • Organizer: 第23回日本消化器関連学会週間 (JDDW2015)
  • Place of Presentation: グランドプリンスホテル新高輪・国際パミール・グランドプリンスホテル高輪（東京都品川区）
  • Year and Date: 2015-10-08