Analysis of the factors of malignant behavior in hepatic progenitor cell marker expressing hepatocellular carcinoma

• Project/Area Number: 15K08990
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Niigata University
• Principal Investigator: Tsuchiya Atsunori 新潟大学, 医歯学総合病院, 助教 (70464005)
• Co-Investigator(Renkei-kenkyūsha): TERAI Shuji 新潟大学, 大学院医歯学総合研究科・消化器内科, 教授 (00332809)
• Research Collaborator: KOJIMA Yuichi ; SEINO Satoshi
• 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 肝細胞癌 / 肝前駆細胞 / EpCAM / NCAM / CK19 / DLK1 / 肝前駆細胞マーカー / 腫瘍マーカー / 幹前駆細胞

Outline of Final Research Achievements

In this study we analyzed the expression of four hepatic progenitor cell markers in 251 hepatocellular carcinomas (HCCs) with their clinical data and tumor markers, and significance of the hepatic progenitor markers in HCC for prognosis. We elucidated that EpCAM expression, DCP>300 mAU/ml, age > 60, Child-Pugh sore grade B or C were independent prognostic factors of poor outcome and were used in a new scoring system for HCC prognosis after operation. Expression of two or more HPC markers was a significant predictor of poor HCC outcome and co-related with AFP and AFP-L3 levels, blood vessel invasion and differentiation of the tumor.

Research Products

• [Journal Article] Clinical outcome of hepatocellular carcinoma can be predicted by the expression of hepatic progenitor cell markers and serum tumour markers (2018)
  • Author(s): Seino Satoshi、Tsuchiya Atsunori、Watanabe Yusuke、Kawata Yuzo、Kojima Yuichi、Ikarashi Shunzo、Yanai Hiroyuki、Nakamura Koji、Kumaki Daisuke、Hirano Masaaki、Funakoshi Kazuhiro、Aono Takashi、Sakai Takeshi、Sakata Jun、Takamura Masaaki、Kawai Hirokazu、Yamagiwa Satoshi、Wakai Toshifumi、Terai Shuji
  • Journal Title: Oncotarget Volume: 9 Issue: 31 Pages: 21844-21860
  • DOI: 10.18632/oncotarget.25074
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Status of and candidates for cell therapy in liver cirrhosis: overcoming the "point of no return" in advanced liver cirrhosis. (2017)
  • Author(s): Terai S, Tsuchiya A.
  • Journal Title: J Gastroenterol. Volume: Feb;52(2) Issue: 2 Pages: 129-140
  • DOI: 10.1007/s00535-016-1258-1
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] An Unusual Case of an Extremely Large α-Fetoprotein-Producing Tumor. (2016)
  • Author(s): Takahashi K, Tsuchiya A, Terai S.
  • Journal Title: Gastroenterology. Volume: Dec;151(6): Issue: 6 Pages: 1077-1080
  • DOI: 10.1053/j.gastro.2016.08.018
  • Peer Reviewed
• [Journal Article] Stomach Dysfunction Is a Potential Risk Factor for Wernicke's Encephalopathy. (2016)
  • Author(s): Nakano O, Tsuchiya A, Yamagiwa S, Terai S.
  • Journal Title: Intern Med. Volume: 55(24) Issue: 24 Pages: 3679-3680
  • DOI: 10.2169/internalmedicine.55.7483
  • NAID: 130005250350
  • Peer Reviewed
• [Journal Article] Improvement of Pancreatic Tumor-induced NAFLD with Pancrelipase (2016)
  • Author(s): Kuraoka N, Tsuchiya A, Suda T, Terai S
  • Journal Title: Internal Medicine Volume: 55 Issue: 1 Pages: 89-90
  • DOI: 10.2169/internalmedicine.55.5729
  • NAID: 130005116798
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A rare pancreatic tumor that underwent a change in morphology and histopathological (2015)
  • Author(s): Seino S, Tsuchiya A, Natsui M
  • Journal Title: Gastroenterology Volume: 150(2) Issue: 2 Pages: e11-e13
  • DOI: 10.1053/j.gastro.2015.06.049
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hepatic progenitor cells of biliary origin with liver repopulation capacity (2015)
  • Author(s): Lu WY, Bird T, Boulter L, Tsuchiya A, Cole A, Hay T, Guest R, Wojtacha D, Man TY, Mackinnon A, Ridgway R, Kendall T, Williams, Jamieson T, Raven A, Hay D, Iredale J, Clarke A, Sansom O, Forbes SJ
  • Journal Title: Nature Cell Biology Volume: 17(8) Issue: 8 Pages: 971-983
  • DOI: 10.1038/ncb3203
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Factors predicting aggressiveness of non-hypervascular hepatic nodules detected on hepatobiliary phase of gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid magnetic resonance imaging (2015)
  • Author(s): Kanefuji T, Takano T, Suda T, Akazawa K, Yokoo T, Kamimura H, Kamimura K, Tsuchiya A, Takamura M, Kawai H, Yamagiwa S, Aoyama H, Nomoto M, Terai S
  • Journal Title: World J Gastroenterol Volume: 21(15) Issue: 15 Pages: 4583-4591
  • DOI: 10.3748/wjg.v21.i15.4583
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 肝前駆細胞マーカー陽性肝細胞癌の臨床的特徴とAFP-L3分画を用いた拾い上げの可能性 (2017)
  • Author(s): 清野智、土屋淳紀、小島雄一、渡邉雄介、阿部聡司、坂牧僚、上村顕也、高村昌昭、川合弘一、山際訓、寺井崇二
  • Organizer: 日本肝臓学会総会
• [Presentation] AFP-L3分画陰性化後の再上昇から肝細胞癌の再発を早期に予知し得た２例 (2016)
  • Author(s): 薛徹、土屋淳紀
  • Organizer: 肝臓学会東部会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2016-12-08
• [Presentation] Significance of hepatic progenitor cell marker-positive hepatocellular carcinoma and its possible prediction by AFP-L3 (2016)
  • Author(s): 土屋淳紀
  • Organizer: AASLD 2016
  • Place of Presentation: ボストン（アメリカ合衆国）
  • Year and Date: 2016-11-11
  • Int'l Joint Research
• [Presentation] Combination therapy with mesenchymal stem cells and macrophages from bone marrow shows favorable outcome in mouse CCl4-induced liver cirrhosis model (2016)
  • Author(s): 渡邉雄介、土屋淳紀
  • Organizer: AASLD 2016
  • Place of Presentation: ボストン（アメリカ合衆国）
  • Year and Date: 2016-11-11
  • Int'l Joint Research
• [Presentation] Comparative effectiveness of mesenchymal stem cell therapy and macrophage cell therapy in a liver cirrhosis disease model (2016)
  • Author(s): 土屋淳紀
  • Organizer: APDW 2016
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
  • Year and Date: 2016-11-02
  • Int'l Joint Research
• [Presentation] 肝硬変の治療メカニズム解析のための骨髄由来のMSC、マクロファージ培養および解析 (2016)
  • Author(s): 土屋淳紀
  • Organizer: 第３７回日本炎症・再生医学会
  • Place of Presentation: みやこめっせ（京都府京都市）
  • Year and Date: 2016-06-16
• [Presentation] 肝幹前駆細胞マーカー陽性肝細胞癌の臨床的意義や腫瘍マーカーとの (2016)
  • Author(s): 土屋淳紀、小島雄一、清野智、渡邉雄介、川田雄三、
  • Organizer: 第15会再生医療学会
  • Place of Presentation: 大阪国際会議場(大阪府、大阪市）
  • Year and Date: 2016-03-19
• [Presentation] Analysis of prognostic significance of hepatic progenitor cell marker-positive hepatocellular carcinoma (2015)
  • Author(s): Tsuchiya A Nomoto M, Terai S
  • Organizer: JDDW日本消化器関連学会週間（２０１５）
  • Place of Presentation: 東京品川プリンスホテル（東京都、港区）
  • Year and Date: 2015-10-08
• [Presentation] 肝幹前駆細胞nicheで再生されるstromal cell derived factor-1(SDF-1)は肝再生促進に関わる (2015)
  • Author(s): 清野 智 土屋 淳紀，寺井 崇二
  • Organizer: JDDW日本消化器関連学会週間
  • Place of Presentation: 東京品川プリンスホテル（東京都、港区）
  • Year and Date: 2015-10-08
• [Book] Gene Therapy and Cell Therapy Through the Liver (2015)
  • Author(s): Tsuchiya A, Forbes SJ
  • Total Pages: 9
  • Publisher: Springer