A fundamental study for construction of PDAC early diagnosis method by DNA methylation analysis.

• Project/Area Number: 15K21247
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology; Experimental pathology
• Research Institution: Kagoshima University
• Principal Investigator: Yokoyama Seiya 鹿児島大学, 医歯学域医学系, 助教 (20569941)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: PDAC / pancreas / MUC1 / MUC4 / prognosis / CA19-9 / DNA methylation / epigenetics / 膵癌 / mucin / 予後予測 / MUC2 / がん / ムチン / 臨床検体解析 / エピジェネティクス / DNAのメチル化解析 / 術後予測 / 膵液 / 悪性度予測

Outline of Final Research Achievements

Pancreatic ductal adenocarcinoma (PDAC) has high frequency of recurrence even if possible to surgery. In this program, we analyzed DNA methylation status of mucin genes using pancreatic tissue with/without tumor to construct marker for predicting prognosis after surgery. The methylation status of MUC1 and MUC4 are statistically associated with clinicopathological information. Our result suggested that MUC1 and MUC4 methylation status has potential for predicted prognosis.

Research Products

• [Int'l Joint Research] ネブラスカ州立大学メディカルセンター(米国)
• [Int'l Joint Research] ウルム大学(ドイツ)
• [Int'l Joint Research] University of Nebraska Medical Center(米国)
• [Int'l Joint Research] University of Ulm(Germany)
• [Journal Article] TET1-mediated DNA hypomethylation regulates the expression of MUC4 in lung cancer (2017)
  • Author(s): Yokoyama, S. Higashi, M. Tsutsumida, H. Wakimoto, J. Hamada, T. Wiest, E. Matsuo, K. Kitazono, I. Goto, Y. Guo, X. Hamada, T. Yamada, S. Hiraki, T. Yonezawa, S. Batra, S. K. Hollingsworth, M. A. Tanimoto, A.
  • Journal Title: Genes & cancer Volume: 8 Issue: 3-4 Pages: 517-527
  • DOI: 10.18632/genesandcancer.139
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Assessment of tumor characteristics based on glycoform analysis of membrane-tethered MUC1 (2017)
  • Author(s): Matsuda, A. Higashi, M. Nakagawa, T. Yokoyama, S. Kuno, A. Yonezawa, S. Narimatsu, H.
  • Journal Title: Lab Invest Volume: 97 Issue: 9 Pages: 1103-1113
  • DOI: 10.1038/labinvest.2017.53
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Immunohistochemical expression of mucin antigens in gallbladder adenocarcinoma: MUC1-positive and MUC2-negative expression Is associated with vessel invasion and shortened survival. (2017)
  • Author(s): Hiraki T, Yamada S, Higashi M, Hatanaka K, Yokoyama S, Kitazono I, Goto Y, Kirishima M, Batra SK, Yonezawa S, Tanimoto A
  • Journal Title: HISTOLOGY & HISTOPATHOLOGY Volume: 32(6) Pages: 585-596
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Aberrant methylation of MUC1 and MUC4 promoters are potential prognostic biomarkers for pancreatic ductal adenocarcinomas (2016)
  • Author(s): Yokoyama, S. Higashi, M. Kitamoto, S. Oeldorf, M. Knippschild, U. Kornmann, M. Maemura, K. Kurahara, H. Wiest, E. Hamada, T. Kitazono, I. Goto, Y. Tasaki, T. Hiraki, T. Hatanaka, K. Mataki, Y. Taguchi, H. Hashimoto, S. Batra, S. K. Tanimoto, A. Yonezawa, S. Hollingsworth, M. A.
  • Journal Title: Oncotarget Volume: - Issue: 27 Pages: 42553-42565
  • DOI: 10.18632/oncotarget.9924
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Mucin expression in endoscopic ultrasound-guided fine-needle aspiration specimens is a useful prognostic factor in pancreatic ductal adenocarcinoma. (2015)
  • Author(s): Higashi M, Yokoyama S, Yamamoto T, Goto Y, Kitazono I, Hiraki T, et al.
  • Journal Title: Pancreas Volume: 44 Issue: 5 Pages: 728-34
  • DOI: 10.1097/mpa.0000000000000362
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 横山 勢也 (2018)
  • Author(s): MUC1およびMUC4のDNAメチル化異常は膵癌切除術後の予後リスクマーカーとなるか
  • Organizer: 第7回 膵勉強会
• [Presentation] Seiya Yokoyama, Michiyo Higashi, Sohsuke Yamada, Taiji Hamada, Akihide Tanimoto (2017)
  • Author(s): Aberrant methylation of MUC1 and MUC4 promoters are potential risk marker for prognosis after surgery of pancreatic ductal adenocarcinomas.
  • Organizer: 14th International Workshop on Carcinoma-associated Mucins
  • Int'l Joint Research
• [Book] 新規DNAメチル化解析法による新しい予後マーカーの開発 (2016)
  • Author(s): 横山勢也、東美智代
  • Publisher: 月刊「化学工業」
• [Remarks] 鹿児島大学大学院医歯学域医学系腫瘍学講座病理学分野
  • URL: http://www2.kufm.kagoshima-u.ac.jp/field/advanced-therapeutics/f107/01.html
• [Remarks] 鹿児島大学 大学院医歯学総合研究科 腫瘍学講座 病理学分野
  • URL: http://www2.kufm.kagoshima-u.ac.jp/field/advanced-therapeutics/f107/01.html
• [Remarks] 鹿児島大学院 医歯学総合研究科 先進治療学専攻 腫瘍学講座 人体がん病理学 (旧第二病理)
  • URL: http://www.kufm.kagoshima-u.ac.jp/~byouri2/