Prediction for HCC development and the effect of statin for NASH patients

• Project/Area Number: 16K19940
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: HIGASHI Takaaki 熊本大学, 医学部附属病院, 非常勤診療医師 (70594878)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 非アルコール性脂肪肝炎（NASH） / 非アルコール性脂肪性肝疾患（NAFLD） / 肝細胞癌 / 発癌予測 / 186 gene signature / スタチン / メタボリックシンドローム / Gene Signature / 薬剤感受性

Outline of Final Research Achievements

Hepatocellular carcinoma (HCC) are developed from the background livers such as viral hepatitis, alcoholic hepatitis, the non-alcoholic steatohepatitis (NASH) fatty liver disease (NAFLD), but the mechanism of HCC development and progress is still unclear. In this study, I focused on NASH and NAFLD patients in particular to identify the carcinogenic risk of HCC and biomarker poor-prognosis for NASH and NAFLD. And also I tried to search a drug (statin in particular) which might improve the prognosis.
It was confirmed that 186 gene signature was useful for the HCC prediction of the NASH, NAFLD patients. In addition, I confirmed statin could induce the apoptosis and have the anti-proliferative effects on HCC cell lines in vitro. In clinical cohort, the patients who took statin showed significantly longer disease free survival than ones who didn’t take statin.

Research Products

• [Journal Article] In vitro modeling of hepatocellular carcinoma molecular subtypes for anti-cancer drug assessment. (2018)
  • Author(s): Hirschfield H, Bian CB, Higashi T, Nakagawa S, Zeleke TZ, Nair VD, Fuchs BC, Hoshida Y.
  • Journal Title: Exp Mol Med. Volume: 50(1) Issue: 1 Pages: e419-e419
  • DOI: 10.1038/emm.2017.164
  • Peer Reviewed
• [Journal Article] Cell type-specific pharmacological kinase inhibition for cancer chemoprevention. (2018)
  • Author(s): Deshmukh M, Nakagawa S, Higashi T, Vincek A, Venkatesh A, Ruiz de Galarreta M, Koh AP, Goossens N, Hirschfield H, Bian CB, Fujiwara N, Ono A, Hoshida H, El-Abtah M, Ahmad NB, Lujambio A, Sanchez R, Fuchs BC, Poelstra K, Prakash J, Hoshida Y.
  • Journal Title: Nanomedicine. Volume: 14(2) Issue: 2 Pages: 317-325
  • DOI: 10.1016/j.nano.2017.11.004
  • Peer Reviewed
• [Journal Article] Hepatic stellate cells as key target in liver fibrosis. (2017)
  • Author(s): Higashi T, Friedman SL, Hoshida Y
  • Journal Title: Adv Drug Deliv Rev. Volume: 121 Pages: 27-42
  • DOI: 10.1016/j.addr.2017.05.007
  • Peer Reviewed
• [Journal Article] Molecular Liver Cancer Prevention in Cirrhosis by Organ Transcriptome Analysis and Lysophosphatidic Acid Pathway Inhibition. (2016)
  • Author(s): Nakagawa S, Higashi T, Goossens N, Bain G, Lauwers GY, Koh AP, El-Abtah M, Ahmad NB, Hoshida H, Erstad DJ, Gunasekaran G, Lee Y, Yu ML, Chuang WL, Dai CY, Baba H, Mahajan M, Nair VD, Lanuti M, Iavarone M, Colombo M, Llovet JM, Tager AM, Schwarz ME, Chung RT, Tanabe KK, Zhang B, Fuchs BC, Hoshida Y, et al.
  • Journal Title: Cancer Cell Volume: 30(6) Issue: 6 Pages: 879-890
  • DOI: 10.1016/j.ccell.2016.11.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Statin attenuates cell proliferative ability via TAZ (WWTR1) in hepatocellular carcinoma. (2016)
  • Author(s): Higashi T, Hayashi H, Kitano Y, Yamamura K, Kaida T, Arima K, Taki K, Nakagawa S, Okabe H, Nitta H, Imai K, Hashimoto D, Chikamoto A, Beppu T, Baba H.
  • Journal Title: Med Oncol. Volume: 33(11) Issue: 11 Pages: 123-123
  • DOI: 10.1007/s12032-016-0845-6
  • Peer Reviewed