Identification of novel mutations of candidate driver genes in immune pathogenesis of hepatocellular carcinoma

• Project/Area Number: 25293171
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: University of Fukui
• Principal Investigator: Nakamoto Yasunari 福井大学, 医学部, 教授 (40293352)
• Co-Investigator(Kenkyū-buntansha): YAMASHITA TARO 金沢大学, 附属病院, 助教 (90377432)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2013: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: 癌 / 遺伝子 / 核酸 / 動物 / 内科

Outline of Final Research Achievements

The current study was designed to identify novel mutations of 119 candidate driver genes in an animal model of immune pathogenesis of hepatocellular carcinoma (HCC). In the tumor tissues, non-synonymous mutations (> 1 %) were detected in the 24 genes and hyper-methylation of CpG islands were observed around the coding region of 7 genes. Gene ontology analysis reveals that these gene changes may be enriched in functions involved in oxidation reduction / mitochondrion / oxidoreductase activity, suggesting the plausible molecular targets for HCC.

Research Products

• [Journal Article] 1.Effect of green tea catechins on gastric mucosal dysplasia in insulin-gastrin mice. (2016)
  • Author(s): Ohno T, Ohtani M, Suto H, Ohta M, Imamura Y, Matsuda H, Hiramatsu K, Nemoto T, Nakamoto Y.
  • Journal Title: Oncol. Rep. Volume: 35 Issue: 6 Pages: 3241-3247
  • DOI: 10.3892/or.2016.4717
  • Peer Reviewed / Open Access
• [Journal Article] High-dose cyclophosphamide induces specific tumor immunity with concomitant recruitment of LAMP1/CD107a-expressing CD4-positive T cells into tumor sites. (2015)
  • Author(s): Naito, T., Baba, T., Takeda, K., Sasaki, S., Nakamoto, Y. and Mukaida, N.
  • Journal Title: Cancer Letters Volume: 366 Issue: 1 Pages: 93-99
  • DOI: 10.1016/j.canlet.2015.06.009
  • NAID: 120005663501
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism: a case report. (2015)
  • Author(s): Tanaka T, Hiramatsu K, Nosaka T, Saito Y, Naito T, Takahashi K, Ofuji K, Matsuda H, Ohtani M, Nemoto T, Suto H, Yamamoto T, Kimura H, Nakamoto Y.
  • Journal Title: BMC Cancer Volume: 15 Issue: 1 Pages: 863-863
  • DOI: 10.1186/s12885-015-1831-7
  • Peer Reviewed / Open Access
• [Journal Article] Defeating EpCAM(+) liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma. (2015)
  • Author(s): Nio K, Yamashita T, Okada H, Kondo M, Hayashi T, Hara Y, Nomura Y, Zeng SS, Yoshida M, Hayashi T, Sunagozaka H, Oishi N, Honda M, Kaneko S
  • Journal Title: J. Hepatology Volume: 5 Issue: 5 Pages: 1164-72
  • DOI: 10.1016/j.jhep.2015.06.009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of microRNAs specific for epithelial cell adhesion molecule-positive tumor cells in hepatocellular carcinoma. (2015)
  • Author(s): Ji J, Zheng X, Forgues M, Yamashita T, Wauthier EL, Reid LM, Wen X, Song Y, Wei JS, Khan J, Thorgeirsson SS, Wang XW.
  • Journal Title: Hepatology Volume: 62 Issue: 3 Pages: 829-840
  • DOI: 10.1002/hep.27886
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] In vivo immunological antitumor effect of OK-432-stimulated dendritic cell transfer after radiofrequency ablation. (2014)
  • Author(s): Nakagawa H, Mizukoshi E, Iida N, Terashima T, Kitahara M, Marukawa Y, KitamuraK, Nakamoto Y, Hiroishi K, Imawari M, Kaneko S
  • Journal Title: Cancer Immunol Immunother. Volume: 63(4) Issue: 4 Pages: 347-356
  • DOI: 10.1007/s00262-013-1514-7
  • NAID: 120005368239
  • Peer Reviewed / Open Access
• [Journal Article] Efficient generation of highly immunocompetent dendritic cells from peripheral blood of patients with hepatitis C virus-related hepatocellular carcinoma. (2014)
  • Author(s): Kitahara M, Mizukoshi E, Nakamoto Y, Mukaida N, Matsushima K, Kaneko S
  • Journal Title: Int. Immunopharmacol. Volume: 21(2) Issue: 2 Pages: 346-353
  • DOI: 10.1016/j.intimp.2014.05.023
  • NAID: 120005463368
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of hepatic arterial infusion chemotherapy and sorafenib in elderly patients with advanced hepatocellular carcinoma. (2014)
  • Author(s): Nemoto T, Matsuda H, Nosaka T, Saito Y, Ozaki Y, Hayama R, Naito T, Takahashi K, Ofuji K, Ohtani M, Hiramatsu K, Suto H, Nakamoto Y
  • Journal Title: Mol. Clin. Oncol. Volume: 2(6) Pages: 1028-1034
  • Peer Reviewed / Open Access
• [Journal Article] Multicenter validation study of anti-programmed cell death-1 antibody as a serological marker for type 1 autoimmune hepatitis. (2014)
  • Author(s): Miyake Y, Yamamoto K, Matsushita H, Abe M, Takahashi A, Umemura T, Tanaka A, Nakamuta M, Nakamoto Y, Ueno Y, Saibara T, Takikawa H, Yoshizawa K, Ohira H, Zeniya M, Onji M, Tsubouchi H; Intractable Liver and Biliary Diseases Study Group of Japan
  • Journal Title: Hepatol Res. Volume: in press Issue: 13 Pages: 1299-1307
  • DOI: 10.1111/hepr.12305
  • Peer Reviewed / Open Access
• [Journal Article] A peptide antigen derived from EGFR T790M is immunogenic in non small cell lung cancer. (2014)
  • Author(s): Ofuji K, Tada Y, Yoshikawa T, Shimomura M, Yoshimura M, Saito K, Nakamoto Y, Nakatsura T
  • Journal Title: Int. J. Oncol. Volume: 46(2) Issue: 2 Pages: 497-504
  • DOI: 10.3892/ijo.2014.2787
  • Peer Reviewed / Open Access
• [Journal Article] Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma. (2014)
  • Author(s): Yamashita T, Kitao A, Matsui O, Hayashi T, Nio K, Kondo M, Ohno N, Miyati T, Okada H, Yamashita T, Mizukoshi E, Honda M, Nakanuma Y, Takamura H, Ohta T, Nakamoto Y, Yamamoto M, Takayama T, Arii S, Wang XW, Kaneko S
  • Journal Title: Hepatology Volume: in press Issue: 5 Pages: 1674-85
  • DOI: 10.1002/hep.27093
  • Peer Reviewed / Open Access
• [Journal Article] Increase in CD14+HLA-DR -/low myeloid-derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis. (2013)
  • Author(s): Arihara F, Mizukoshi E, Kitahara M, Takata Y, Arai K, Yamashita T, Nakamoto Y, Kaneko S
  • Journal Title: Cancer Immunol Immunother. Volume: 62(8) Issue: 8 Pages: 1421-1430
  • DOI: 10.1007/s00262-013-1447-1
  • Peer Reviewed
• [Journal Article] Discrete nature of EpCAM(+) and CD90(+) cancer stem cells in human hepatocellular carcinoma. (2013)
  • Author(s): Yamashita T, Nakamoto Y, et al.
  • Journal Title: Hepatology Volume: 57 Issue: 4 Pages: 1484-1497
  • DOI: 10.1002/hep.26168
  • Peer Reviewed
• [Presentation] Chemokine CCL3/CCR5-recruited, Cytotoxic CD4+ T Cells Eradicate Hepatoma Cells in a Model of Anticancer Chemotherapy with High-Dose Cyclophosphamide. (2015)
  • Author(s): Naito T, Baba T, Takeda K, Sasaki S, Mukaida N, Nakamoto Y.
  • Organizer: The 66th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD2015)
  • Place of Presentation: San Francisco, U.S.A.
  • Year and Date: 2015-11-17
  • Int'l Joint Research
• [Presentation] Identification of Hypermethylation and Non-Synonymous Mutations in Genes Down-Regulated during the Process of Hepatocarcinogenesis in a Model of Chronic Hepatitis B. (2014)
  • Author(s): Nakamoto Y, Yamashita T, Hiramatsu K, Nemoto T, Suto H, Kaneko S
  • Organizer: The 65th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2014)
  • Place of Presentation: Boston, Massachusetts
  • Year and Date: 2014-11-09
• [Presentation] Clinical evaluation of patency capsule system in high risk patients for video capsule endoscopy.
  • Author(s): Ohtani M, Suto H, Nakamoto Y
  • Organizer: Japan Digestive Disease Week 2013
  • Place of Presentation: Grand Prince Hotel New Takanawa, Tokyo