Radiogenomics of hepatocellular carcinoma based on molecular and genetic classification

• Project/Area Number: 17K10354
• 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: Kitao Azusa 金沢大学, 附属病院, 講師 (20608690)
• Co-Investigator(Kenkyū-buntansha): 蒲田 敏文 金沢大学, 医学系, 教授 (00169806) ; 原田 憲一 金沢大学, 医学系, 教授 (30283112)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肝細胞癌 / Radiogenomics / Dynamic CT / Gd-EOB-DTPA造影MRI / EOB-MRI / P53 / CT / MRI / radiogenomics / Gd-EOB-DTPA

Outline of Final Research Achievements

β-catenin activated HCC showed increased enhancement ratio in the hepatobiliary phase of Gd-EOB-DTPA enhanced MRI in case of co-expression of hepatocyte nuclear factor (HNF) 4α. Co-expression of β-catenin and HNF4α would be the main mechanism inducing both OATP1B3 expression and less aggressive biological natures in this subtype of HCC.
P53 mutated HCC showed significantly higher level of serum tumor markers, poorer differentiation grade and poorer survival rate after resection. Imaging features of intra-tumoral dilated arteries in the arterial phase of dynamic CT, and low signal intensity ratio in the hepatobiliary phase of EOB-MRI would be the independent predictors of this aggressive subtype.

Academic Significance and Societal Importance of the Research Achievements

肝細胞癌の分子遺伝子発現が画像診断により推測することができれば、侵襲的な組織採取を行わずに悪性度や予後の推測が可能となり、個別化診療の時代において重要な役割を果たすものと考えられる。

Research Products

• [Journal Article] Gadoxetic acid enhanced MR imaging for hepatocellular carcinoma: molecular and genetic background. (2020)
  • Author(s): Kitao A, Matsui O, Yoneda N, Kozaka K, Kobayashi S, Koda W, Inoue D, Ogi T, Yoshida K, Gabata T.
  • Journal Title: European Radiology Volume: Epub ahead of print Issue: 6 Pages: 3438-3447
  • DOI: 10.1007/s00330-020-06687-y
  • Peer Reviewed
• [Journal Article] Current status of imaging biomarkers predicting the biological nature of hepatocellular carcinoma. (2019)
  • Author(s): Yoneda N, Matsui O, Kobayashi S, Kitao A, Kozaka K, Inoue D, Yoshida K, Minami T, Koda W, Gabata T
  • Journal Title: Jpn J Radiol Volume: 37 Issue: 3 Pages: 191-208
  • DOI: 10.1007/s11604-019-00817-3
  • NAID: 50013182407
  • Peer Reviewed
• [Journal Article] Differentiation Between Hepatocellular Carcinoma Showing Hyperintensity on the Hepatobiliary Phase of Gadoxetic Acid-Enhanced MRI and Focal Nodular Hyperplasia by CT and MRI. (2018)
  • Author(s): Kitao A, Matsui O, Yoneda N, Kita R, Kozaka K, Kobayashi S, Gabata S
  • Journal Title: AJR American journal of roentgenology Volume: 211 Issue: 2 Pages: 347-57
  • DOI: 10.2214/ajr.17.19341
  • Peer Reviewed
• [Journal Article] Gadoxetic acid-enhanced magnetic resonance imaging reflects co-activation of β-catenin and hepatocyte nuclear factor 4α in hepatocellular carcinoma. (2018)
  • Author(s): Kitao A, Matsui O, Yoneda N, Kozaka K, Kobayashi S, Koda W, Minami T, Inoue D, Yoshida K, Yamashita T, Yamashita T, Kaneko S, Takamura H, Ohta T, Ikeda H, Sato Y, Nakanuma Y, Harada K, Kita R, Gabata T.
  • Journal Title: Hepatology Research Volume: 48 Issue: 2 Pages: 205-216
  • DOI: 10.1111/hepr.12911
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Differentiation between hepatocellular carcinoma showing hyperintensity on the hepatobiliary phase of gadoxetic acid enhanced MRI and focal nodular hyperplasia by CT and MRI (2018)
  • Author(s): Kitao A, Matsui O, Yoneda N, Kita R, Kozaka K, Kobayashi S, Gabata T
  • Journal Title: American Journal of Roentgenology Volume: in press
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 肝細胞癌の画像バイオマーカーとしてのEOB-MRI (2020)
  • Author(s): 北尾 梓
  • Organizer: 第33回JCRミッドウィンターセミナー
  • Invited
• [Presentation] Imaging features of dysplastic nodule, early hepatocellular carcinoma and small well differentiated hepatocellular carcinoma correlated with pathological findings. (2019)
  • Author(s): Azusa Kitao, e, Osamu Matsui, Norihide Yoneda, Kazuto Kozaka, Satoshi Kobayashi, Wataru Koda, Dai Inoue, Kotaro Yoshida, Toshifumi Gabata
  • Organizer: The 78th Japanese Congress of Radiology
• [Presentation] Imaging characteristics of spontaneous regression of hepatocellular carcinoma (2019)
  • Author(s): Azusa Kitao, Norihide Yoneda, Kazuto Kozaka, Satoshi Kobayashi, Osamu Matsui, Toshifumi Gabata
  • Organizer: European Society of Gastrointestinal Abdominal Radiology
  • Int'l Joint Research
• [Presentation] 異型結節、早期肝細胞癌、小型高分化型肝細胞癌の画像所見の検討 (2019)
  • Author(s): 北尾 梓, 松井 修, 米田憲秀, 小坂一斗, 小林 聡, 蒲田敏文
  • Organizer: 第55回日本肝癌研究会
• [Presentation] 肝細胞癌自然退縮の画像所見の検討 (2019)
  • Author(s): 51.北尾 梓, 米田憲秀, 小坂一斗, 小林 聡, 松井 修, 蒲田敏文
  • Organizer: 第25回肝血流動態・機能イメージ研究会
• [Presentation] Gd-EOB-DTPA 造影 MRI 読影のコツと注意点 (2018)
  • Author(s): 北尾 梓, 松井 修, 米田憲秀, 小坂一斗, 小林 聡, 香田 渉, 南 哲弥, 井上 大, 吉田耕太郎, 蒲田敏文.
  • Organizer: 第77回日本医学放射線学会総会
• [Presentation] 肝細胞癌の画像バイオマーカーとしてのEOB-MRI (2018)
  • Author(s): 北尾 梓、松井 修、米田憲秀、小坂一斗、小林 聡、山下太郎、山下竜也、金子周一、原田憲一、蒲田敏文
  • Organizer: 第54回肝癌研究会
• [Presentation] EOB-MRI肝細胞相高信号肝細胞癌と限局性結節性過形成との鑑別 (2018)
  • Author(s): 北尾 梓、松井 修、米田憲秀、喜多竜一、 小坂一斗、小林 聡、蒲田敏文
  • Organizer: 第54回肝癌研究会
• [Presentation] Diagnosis of hypervascular hepatocellular carcinoma by EOB-MRI -Detection, characterization and as an imaging biomarker- (2018)
  • Author(s): 北尾 梓
  • Organizer: 第46回日本磁気共鳴医学会大会
  • Invited
• [Presentation] Gadoxetic acid enhanced MRI for the diagnosis of hepatocellular carcinoma: Knack and pitfalls (2018)
  • Author(s): Azusa Kitao, Osamu Matsui, Norihide Yoneda, Kazuto Kozaka, Satoshi Kobayashi, Wataru Koda, Dai Inoue, Hiroyuki Aburano, Takahiro Ogi, Kotaro Yoshida, Toshifumi Gabata
  • Organizer: 104th Radiological Society of North America
  • Int'l Joint Research
• [Presentation] Imaging of hepatic periportal lesions and perivenous lesions (2018)
  • Author(s): Azusa Kitao, Osamu Matsui, Norihide Yoneda, Kazuto Kozaka, Satoshi Kobayashi, Wataru Koda, Dai Inoue, Hiroyuki Aburano, Takahiro Ogi, Kotaro Yoshida, Toshifumi Gabata
  • Organizer: 104th Radiological Society of North America
  • Int'l Joint Research
• [Presentation] Differentiation between hepatocellular carcinoma showing uptake of gadoxetic acid and focal nodular hyperplasla (2018)
  • Author(s): A Kitao, Matsui O, Yoneda N, Kita R, Kozaka K, Kobayashi S, Gabata T
  • Organizer: European Congress of Radiology 2018
  • Int'l Joint Research
• [Presentation] Gadoxetic acid-enhanced MR imaging reflects coactivation of β-catenin and hepatocyte nuclear factor 4αin HCC (2017)
  • Author(s): A Kitao, Matsui O, Yoneda N, Kita R, Kozaka K, Kobayashi S, Koda W, Minami T, Inoue D, Ogi T, Yoshida K, Gabata T
  • Organizer: European Society of Gastrointestial and Abdominal Radiology
  • Int'l Joint Research
• [Presentation] OATP１B3陽性（EOB-MRI肝細胞相高信号）肝細胞癌のCT/MRI所見の特徴の再検討 (2017)
  • Author(s): 北尾 梓、松井 修、米田憲秀、小坂一斗、小林 聡、蒲田敏文
  • Organizer: 第53回日本肝癌研究会
• [Presentation] OATP1B3陽性肝細胞癌の画像所見の特徴 (2017)
  • Author(s): 北尾 梓、松井 修、米田憲秀、小坂一斗、小林 聡、吉田耕太郎、井上 大、南 哲弥、香田 渉、蒲田敏文
  • Organizer: 第76回日本医学放射線学会総会
• [Presentation] 肝発癌のバイオマーカーとしてのEOB-MRI (2017)
  • Author(s): 北尾 梓
  • Organizer: 第76回日本医学放射線学会総会
  • Invited