Attempt to establishment of early diagnosis and prediction of therapeutic response in pancreatobiliary neoplasms

• Project/Area Number: 15K08349
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Kagoshima University
• Principal Investigator: HIGASHI Michiyo 鹿児島大学, 医歯学域附属病院, 准教授 (60315405)
• Co-Investigator(Kenkyū-buntansha): 横山 勢也 鹿児島大学, 医歯学域医学系, 助教 (20569941)
• Research Collaborator: MATSUO KEI 鹿児島大学, 大学院医歯学総合研究科, 技術職員
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 病理学 / 膵胆道腫瘍 / ムチン抗原 / 予後因子 / MUC1 / MUC4 / MUC16 / メチル化 / MUC / methylation / prognosis / 膵胆道系腫瘍 / 病理

Outline of Final Research Achievements

We had reported that expression profiles of mucins are closely associated with biological behavior of human pancreatobiliary neoplasms. We evaluated the methylation status of MUC1 and MUC4 promoter regions in pancreatic tissue samples by the methylation specific electrophoresis (MSE) method. We show that the DNA methylation status of the promoters of MUC1 and MUC4 in pancreatic tissue correlates with the expression of MUC1 and MUC4 mRNA. In addition, the expression of several DNA methylation/demethylation factors show a significant correlation with MUC1 and MUC4 methylation status. Furthermore, CAIX expression significantly correlates with the expression of MUC1 and MUC4. Interestingly, our results indicate that low methylation of MUC1 and/or MUC4 promoters correlates with decreased overall survival. Analysis of epigenetic changes in mucin genes may be of diagnostic utility and one of the prognostic predictors for patients with PDAC.

Research Products

• [Int'l Joint Research] University of Nebraska Medical Center(米国)
• [Int'l Joint Research] University of Ulm(Germany)
• [Int'l Joint Research] University of Nebraska Medical Center(米国)
• [Int'l Joint Research] University of Ulm(Germany)
• [Journal Article] 集学的治療で完全奏効が得られた肝転移を伴うcStage IV膵体部癌の1例 (2018)
  • Author(s): 伊地知, 徹也 蔵原, 弘 前村, 公成 又木, 雄弘 川崎, 洋太 迫田, 雅彦 飯野, 聡 上野, 真一 新地, 洋之 東, 美智代 夏越, 祥次
  • Journal Title: 日本消化器外科学会雑誌 Volume: 50 Pages: 897-904
  • NAID: 130006210157
  • Peer Reviewed
• [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, S. K. Yonezawa, S. Tanimoto, A.
  • Journal Title: Histol Histopathol Volume: 32 Pages: 585-596
  • Peer Reviewed
• [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] Diagnostic efficacy of liquid-based cytology for solid pancreatic lesion samples obtained with endoscopic ultrasound-guided fine-needle aspiration: Propensity score-matched analysis (2017)
  • Author(s): Hashimoto, S. Taguchi, H. Higashi, M. Hatanaka, K. Fujita, T. Iwaya, H. Nakazawa, J. Arima, S. Iwashita, Y. Sasaki, F. Nasu, Y. Kanmura, S. Ido, A.
  • Journal Title: Digestive endoscopy Volume: 29 Issue: 5 Pages: 608-616
  • DOI: 10.1111/den.12827
  • Peer Reviewed / Open Access
• [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] Assessment of tumor characteristics based on glycoform analysis of membrane-tethered MUC1 (2017)
  • Author(s): Atsushi Matsuda, Michiyo Higashi, Tomomi Nakagawa, Seiya Yokoyama, Atsushi Kuno, Suguru Yonezawa, and Hisashi Narimatsu
  • Journal Title: Laboratory Investigation Volume: 印刷中
  • Peer Reviewed / Open Access
• [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] Dexamethasone Suppression FDG PET/CT for Differentiating between True- and False-Positive Pulmonary and Mediastinal Lymph Node Metastases in Non-Small Cell Lung Cancer: A Pilot Study of FDG PET/CT after Oral Administration of Dexamethasone (2016)
  • Author(s): Nakajo, M. Nakajo, M. Nakayama, H. Jinguji, M. Nakabeppu, Y. Higashi, M. Nakamura, Y. Sato, M. Yoshiura, T.
  • Journal Title: Radiology Volume: 279 Issue: 1 Pages: 246-253
  • DOI: 10.1148/radiol.2015150883
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pancreatic hamartoma: a case report and literature review. (2016)
  • Author(s): Matsushita D, Kurahara H, Mataki Y, Maemura K, Higashi M, Iino S, et al.
  • Journal Title: BMC gastroenterology. Volume: 16 Issue: 1 Pages: 419-422
  • DOI: 10.1186/s12876-016-0419-2
  • Peer Reviewed / Open Access
• [Journal Article] Computed tomography and magnetic resonance imaging features of lipid-rich neuroendocrine tumors of the pancreas (2015)
  • Author(s): Fukukura Y, Shindo T, Higashi M, Takumi K, Umanodan T, Yoneyama T, et al.
  • Journal Title: World journal of gastroenterology : WJG Volume: 21 Issue: 34 Pages: 10008-17
  • DOI: 10.3748/wjg.v21.i34.10008
  • Peer Reviewed / Open Access
• [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
• [Journal Article] Pancreatic neuroendocrine tumors: Correlation between the contrast-enhanced computed tomography features and the pathological tumor grade. (2015)
  • Author(s): Takumi K, Fukukura Y, Higashi M, Ideue J, Umanodan T, Hakamada H, et al.
  • Journal Title: Eur J Radiol. Volume: 84 Issue: 8 Pages: 1436-43
  • DOI: 10.1016/j.ejrad.2015.05.005
  • Peer Reviewed / Open Access
• [Presentation] 粘膜類表皮癌においてMUC4とMUC6の発現低下から生存期間の短縮が予想される (2017)
  • Author(s): 本庄, 希江 山口, 壮亮 平木, 翼 東, 美智代 吉村, 卓也 中村, 典史 野元, 三治 野口, 紘嗣 米澤, 傑 谷本, 昭英
  • Organizer: 日本病理学会
• [Presentation] Analysis of Mucin expression and DNA methylation in serous adenoma of the pancreas (2016)
  • Author(s): Michiyo Higashi, Seiya Yokoyama, Tsubasa Hiraki , Ikumi Kitazono, Yuko Goto,Tasaki Takashi, Mari Kirishima, Kazuhito Hatanaka, and Akihide Tanimoto
  • Organizer: 日本病理学会第105回総会
  • Place of Presentation: 仙台国際センター(宮城県仙台市)
  • Year and Date: 2016-05-12
• [Presentation] ムチン発現からみたIPMNの悪性度 (2015)
  • Author(s): 東美智代、横山勢也、北薗育美、後藤優子、田崎貴嗣、平木翼、畑中一仁、蔵原弘、又木雄弘、前村公成、新地洋之、谷本昭英、米澤傑、夏越祥次
  • Organizer: 外科病理学会
  • Place of Presentation: ホテルアパローム紀ノ国(和歌山県和歌山市)
  • Year and Date: 2015-11-06
  • Invited
• [Presentation] 浸潤性膵管癌におけるEUS-FNAでのムチン発現 (2015)
  • Author(s): 東美智代、後藤優子、米澤傑
  • Organizer: 肝胆膵外科学会
  • Place of Presentation: ホテルグランパシフィックLE DAIBA (東京都千代田区)
  • Year and Date: 2015-06-11
• [Presentation] 膵漿液性腫瘍の病理 (2015)
  • Author(s): 東美智代
  • Organizer: 日本病理学会
  • Place of Presentation: 名古屋国際会議場(愛知県名古屋市)
  • Year and Date: 2015-04-30
  • Invited