Correlation between molecular biomarker and imaging findings in hepatocellular carcinoma

• Project/Area Number: 25461805
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Kanazawa University
• Principal Investigator: Matsui Osamu 金沢大学, 医薬保健学総合研究科, 特任教授 (10019961)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Satoshi 金沢大学, 大学院医薬保健学総合研究科, 教授 (30313638) ; Kozaka Kazuto 金沢大学, 大学院医薬保健学総合研究科, 助教 (80547175)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 肝細胞癌 / Gd-EOB-DTPA造影MRI / OATP1B3 / b-catenin mutation / HNF4a / 個別化医療 / β-caenin mutation / ＨＮＦ4α / 肝癌類似病変 / 画像バイオマーカー / 肝細胞がん / 肝癌多段階発癌 / 肝癌境界病変 / dynamic CT

Outline of Final Research Achievements

The significant positive correlation between grades of OATP1B3 expression and enhancement ratio on hepatobiliary phase of Gd-EOB-DTPA enhanced MR imaging in hepatocellular carcinoma (HCC) was verified in this study. In addition, the highly significant correlation between HNF4a, b-catenin and OATP1B3 expression in HCC cells was also revealed. These results made it possible to sub-classify HCCs, resulting in possible application for future personalized medicine in the patient s with HCCs easily in daily practice.

Research Products

• [Journal Article] "Biliary Diseases with Pancreatic Counterparts": Cross-sectional Imaging Findings. (2016)
  • Author(s): Katabathina VS, Flaherty EM, Dasyam AK, Menias CO, Riddle ND, Lath N, Kozaka K, Matsui O, Nakanuma Y, Prasad SR.
  • Journal Title: Radiographics Volume: 29
  • Peer Reviewed / Open Access
• [Journal Article] Morphometric changes in liver cirrhosis: aetiological differences correlated with progression (2016)
  • Author(s): Ozaki K, Matsui O, Kobayashi S, Minami T, Kitao A, Gabata T
  • Journal Title: Br J Radiol. Volume: 89 Pages: 20150896-20150896
  • DOI: 10.1259/bjr.20150896
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Treatment of Liver Tumors with Lipiodol TACE: Technical Recommendations from Experts Opinion. (2016)
  • Author(s): de Baere T, Arai Y, Lencioni R, Geschwind JF, Rilling W, Salem R, Matsui O, Soulen MC.
  • Journal Title: Cardiovasc Intervent Radiol. Volume: 39 Pages: 334-343
  • DOI: 10.1007/s00270-015-1208-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel Imaging Diagnosis for Hepatocellular Carcinoma: Consensus from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014) (2015)
  • Author(s): Chen BB, Murakami T, Shih TT, Sakamoto M, Matsui O, Choi BI, Kim MJ, Lee JM, Yang RJ, Zeng MS, Chen RC, Liang JD.
  • Journal Title: Liver Cancer Volume: 4 Pages: 215-227
  • DOI: 10.1159/000367742
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Correlation between Gd-EOB-DTPA-enhanced MR imaging findings and OATP1B3 expression in chemotherapy-associated sinusoidal obstruction syndrome. (2015)
  • Author(s): Yoneda N, Matsui O, Ikeno H, Inoue D, Yoshida K, Kitao A, Kozaka K, Kobayashi S, Gabata T, Ikeda H, Nakamura K, Ohta T.
  • Journal Title: Abdom Imaging Volume: 40 Pages: 3099-3103
  • DOI: 10.1007/s00261-015-0503-z
  • Peer Reviewed / Open Access
• [Journal Article] Hepatitis C Related Chronic Liver Cirrhosis: Feasibility of Texture Analysis of MR Images for Classification of Fibrosis Stage and Necroinflammatory Activity Grade. (2015)
  • Author(s): Wu Z, Matsui O, Kitao A, Kozaka K, Koda W, Kobayashi S, Ryu Y, Minami T, Sanada J, Gabata T.
  • Journal Title: PLoS One Volume: １０
  • DOI: 10.1371/journal.pone.0118297
  • Peer Reviewed / Open Access
• [Journal Article] Hepatocellular Carcinoma with β-Catenin Mutation: Imaging and Pathologic Characteristics. (2015)
  • Author(s): Kitao A, Matsui O, Yoneda N, Kozaka K, Kobayashi S, Sanada J, Koda W, Minami T, Inoue D, Yoshida K, Yamashita T, Yamashita T, Kaneko S, Takamura H, Ohta T, Ikeda H, Nakanuma Y, Kita R, Gabata T.
  • Journal Title: Radiology Volume: 275 Pages: 708-17
  • DOI: 10.1148/radiol.14141315
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma: The Japan Society of Hepatology 2013 update (3rd JSH-HCC Guidelines). (2015)
  • Author(s): Kokudo N, Hasegawa K, Akahane M, Igaki H, Izumi N, Ichida T, Uemoto S, Kaneko S, Kawasaki S, Ku Y, Kudo M, Kubo S, Takayama T, Tateishi R, Fukuda T, Matsui O, Matsuyama Y, Murakami T, Arii S, Okazaki M, Makuuchi M.
  • Journal Title: Hepatol Res. Volume: 45 Pages: 123-127
  • DOI: 10.1111/hepr.12464
  • Peer Reviewed / Open Access
• [Journal Article] Clinicopathological characteristics of serum amyloid A-positive hepatocellular neoplasms/nodules arising in alcoholic cirrhosis (2015)
  • Author(s): Sasaki M, Yoneda N, Sawai Y, Imai Y, Kondo F, Fukusato T, Yoshikawa S, Kobayashi S, Sato Y, Matsui O, Nakanuma Y.
  • Journal Title: Histopathology Volume: 66 Pages: 836-845
  • DOI: 10.1111/his.12588
  • Peer Reviewed / Open Access
• [Journal Article] Hepatocellular Carcinoma with β-Catenin Mutation: Imaging and Pathologic Characteristics. (2015)
  • Author(s): Kitao A, Matsui O, Yoneda N, Kozaka K, Kobayashi S, Sanada J, Koda W, Minami T, Inoue D, Yoshida K, Yamashita T, Yamashita T, Kaneko S, Takamura H, Ohta T, Ikeda H, Nakanuma Y, Kita R, Gabata T
  • Journal Title: Radiology Volume: Feb. 6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Peretinoin after curative therapy of hepatitis C-related hepatocellular carcinoma: a randomized double-blind placebo-controlled study. (2015)
  • Author(s): Okita K, Izumi N, Matsui O, Tanaka K, Kaneko S, Moriwaki H, Ikeda K, Osaki Y, Numata K, Nakachi K, Kokudo N, Imanaka K, Nishiguchi S, Okusaka T, Nishigaki Y, Shiomi S, Kudo M, Ido K, Karino Y, Hayashi N, Ohashi Y, Makuuchi M, Kumada H
  • Journal Title: J Gastroenterol Volume: 50 Pages: 191-202
  • DOI: 10.1007/s00535-014-0956-9
  • Peer Reviewed / Open Access
• [Journal Article] Oncology (2014)
  • Author(s): Kudo M, Matsui O, Izumi N, Iijima H, Kadoya M, Imai Y; Liver Cancer Study Group of Japan. Surveillance and diagnostic algorithm for hepatocellular carcinoma proposed by the Liver Cancer Study Group of Japan: 2014 update.
  • Journal Title: Oncology Volume: 87 Pages: 7-21
  • Peer Reviewed / Open Access
• [Journal Article] Clinicopathological characteristics of serum amyloid A-positive hepatocellular neoplasms/nodules arising in alcoholic cirrhosis. (2014)
  • Author(s): Sasaki M, Yoneda N, Sawai Y, Imai Y, Kondo F, Fukusato T, Yoshikawa S, Kobayashi S, Sato Y, Matsui O, Nakanuma Y.
  • Journal Title: Histopathology. Volume: Oct. 15
  • 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 Pages: 1674-1685
  • DOI: 10.1002/hep.27093
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hemodynamics and progression of a hypervascular focus in a borderline lesion of hepatocellular carcinoma: analysis by angiography-assisted CT and histopathology (2014)
  • Author(s): Endo T, Kozaka K, Kobayashi S, Sanada J, Koda W, Minami T, Kitao A, Yoneda N, Nakanuma Y, Gabata T, Matsui O.
  • Journal Title: Japanese Journal of Radiology Volume: 32 Issue: 2 Pages: 69-79
  • DOI: 10.1007/s11604-013-0268-7
  • NAID: 210000174825
  • ISSN: 1867-1071, 1867-108X
  • Peer Reviewed
• [Journal Article] Peretinoin after curative therapy of hepatitis C-related hepatocellular carcinoma: a randomized double-blind placebo-controlled study (2014)
  • Author(s): Okita K, Izumi N, Matsui O, Tanaka K, Kaneko S, Moriwaki H, Ikeda K, Osaki Y, Numata K, Nakachi K, Kokudo N, Imanaka K, Nishiguchi S, Okusaka T, Nishigaki Y, Shiomi S, Kudo M, Ido K, Karino Y, Hayashi N, et al
  • Journal Title: J of Gastroenterol. Volume: on-line
  • Peer Reviewed
• [Journal Article] Hypervascular hepatocellular carcinomas showing hyperintensity on hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging: a possible subtype with mature hepatocyte nature. (2013)
  • Author(s): Yoneda N, Matsui O, Kitao A, Kita R, Kozaka K, Koda W, Kobayashi S, Gabata T, Ikeda H, Nakanuma Y
  • Journal Title: Japanese Journal of Radiology Volume: 31 Issue: 7 Pages: 480-490
  • DOI: 10.1007/s11604-013-0224-6
  • NAID: 50008757963
  • ISSN: 1867-1071, 1867-108X
  • Peer Reviewed
• [Journal Article] Evaluation of eligibility criteria in living donor liver transplantation for hepatocellular carcinoma byα-SMA -positive cancer-associated fibroblasts (2013)
  • Author(s): Takamura H, Arai K, 他27名
  • Journal Title: Oncol Rep Volume: 30(4) Pages: 1561-74
  • DOI: 10.3892/or.2013.2616
  • Peer Reviewed
• [Presentation] epatobiliary Phase of Gadoxetic Acid Enhanced MR Imaging of Benign Hepatocellular Nodules: Based on Molecule Background. (2015)
  • Author(s): Norihide Yoneda, Osamu Matsui
  • Organizer: RSNA (Radiological Society of North America)
  • Place of Presentation: シカゴ（米国）
  • Year and Date: 2015-11-30
  • Int'l Joint Research
• [Presentation] A tumor suppression factor HNF4a (hepatocyte nuclear factor) expression correlates with gadoxetic acid enhanced MRI findings in hepatocellular carcinoma. (2015)
  • Author(s): Azusa Kitao, Osamu Matsui
  • Organizer: RSNA (Radiological Society of North America).
  • Place of Presentation: シカゴ（米国）
  • Year and Date: 2015-11-30
  • Int'l Joint Research
• [Presentation] Gd-EOB-DTPA enhanced MRI as an imaging biomarker for activation of beta-catenin signaling in hepatocellular tumor/hyperplasia. (2015)
  • Author(s): Osamu Matsui
  • Organizer: The 6th Asia－Pacific Primary Liver Cancer Expert Meeting (APPLE 2015)
  • Place of Presentation: 大阪
  • Year and Date: 2015-07-03
  • Int'l Joint Research / Invited
• [Presentation] Signal intensity on HB phase in HCCs: Correlation with grade of differentiation, biological nature and molecular expression. (2015)
  • Author(s): Osamu Matsui
  • Organizer: The 6th Asia－Pacific Primary Liver Cancer Expert Meeting (APPLE 2015)
  • Place of Presentation: 大阪
  • Year and Date: 2015-07-03
  • Int'l Joint Research / Invited
• [Presentation] Molecular/genetic mechanism of Gd-EOB-DTPA enhanced MRI for hepatocellular carcinoma: From early diagnosis to personalized medicine (2015)
  • Author(s): Osamu Matsui
  • Organizer: 5th Asian Congress of Abdominal Radiology (ACAR 2015)
  • Place of Presentation: 浜松
  • Year and Date: 2015-06-20
  • Int'l Joint Research / Invited
• [Presentation] Gd-EOB-DTPA enhanced MRI for HCC: Molecular and genetic aspects (2015)
  • Author(s): Matsui O
  • Organizer: ISRS2015
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2015-02-14
  • Invited
• [Presentation] Adovances in imaging modalities for HCC (2015)
  • Author(s): Matsui O
  • Organizer: ewalt（Eastern&Western Association Liver Tumors)
  • Place of Presentation: Milan, italy
  • Year and Date: 2015-01-22 – 2015-01-24
  • Invited
• [Presentation] Molecular Backgrounds of Gd-EOB-DTPA Enhanced MRI in Pathological Early HCC (2014)
  • Author(s): Matsui O
  • Organizer: 第4回国際肝癌シンポジウムKYOTO
  • Place of Presentation: 京都
  • Year and Date: 2014-06-07 – 2014-06-08
  • Invited
• [Presentation] Proposal of New Diagnostic Algorithm Based on Gd-EOB-DTPA Enhanced MRI (2014)
  • Author(s): Ｍａｔｓｕｉ Ｏ
  • Organizer: 第4回国際肝癌シンポジウムKYOTO
  • Place of Presentation: 京都
  • Year and Date: 2014-06-07 – 2014-06-08
  • Invited
• [Presentation] Visualization of multistep hepatocarcinogenesis using various imaging biomarkers (2014)
  • Author(s): Kobayashi S, Gabata T, Matsui O, Koda W, Minami T, Kozaka K, Yoneda N, Yoshida K
  • Organizer: Europian Congress of Radiology
  • Place of Presentation: Viena, Austria
• [Presentation] maging diagnosis of multistep hepatocarcinogenesis (2013)
  • Author(s): 松井 修
  • Organizer: ISTANBUL LIVER IMAGIN MEETING
  • Place of Presentation: Istanbul、 Turkey
  • Invited
• [Presentation] HCC diagnosis and role of transport mechanisms (2013)
  • Author(s): 松井 修
  • Organizer: European society of gastrointestinal and abdominal radiology meeting
  • Place of Presentation: Barcelona, Spain
  • Invited
• [Book] 肝動脈化学塞栓療法(TACE) (2015)
  • Author(s): 松井 修、宮山士朗、大須賀慶悟、衣袋健司
  • Total Pages: 238
  • Publisher: 医学書院