钆塞酸二钠增强磁共振成像反映了β-连环蛋白和肝细胞核因子4α在肝细胞癌中的共同激活。
Gadoxetic acid-enhanced magnetic resonance imaging reflects co-activation of β-catenin and hepatocyte nuclear factor 4α in hepatocellular carcinoma.
作者信息
Kitao Azusa, Matsui Osamu, Yoneda Norihide, Kozaka Kazuto, Kobayashi Satoshi, Koda Wataru, Minami Tetsuya, Inoue Dai, Yoshida Kotaro, Yamashita Taro, Yamashita Tatsuya, Kaneko Shuichi, Takamura Hiroyuki, Ohta Tetsuo, Ikeda Hiroko, Sato Yasunori, Nakanuma Yasuni, Harada Kenichi, Kita Ryuichi, Gabata Toshifumi
机构信息
Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Department of Gastroenterology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
出版信息
Hepatol Res. 2018 Feb;48(2):205-216. doi: 10.1111/hepr.12911. Epub 2017 Jun 13.
AIM
The aim of this study is to clarify the correlation of the co-activation of β-catenin and hepatocyte nuclear factor (HNF)4α with the findings of gadoxetic acid-enhanced magnetic resonance imaging (MRI), organic anion transporting polypeptide (OATP)1B3 expression, and histological findings in hepatocellular carcinoma (HCC).
METHODS
One hundred and ninety-six HCCs surgically resected from 174 patients were enrolled in this study. The HCCs were classified into four groups by immunohistochemical expression of β-catenin, glutamine synthetase (GS), and HNF4α: (i) β-catenin/GS (positive [+]) HNF4α (+); (ii) β-catenin/GS (+) HNF4α (negative [-]); (iii) β-catenin/GS (-) HNF4α (+); and (iv) β-catenin/GS (-) HNF4α (-). We compared the four groups in terms of the enhancement ratio on the hepatobiliary phase of gadoxetic acid-enhanced MRI, immunohistochemical organic anion transporter polypeptide (OATP)1B3 (a main uptake transporter of gadoxetic acid) expression and histological features, overall survival, and no recurrence survival. The Kruskal-Wallis test, Steel-Dwass multiple comparisons test, Fisher's exact test, and log-rank (Mantel-Cox) test were used for statistical analyses.
RESULTS
Enhancement ratio on gadoxetic acid-enhanced MRI in HCC with β-catenin/GS (+) HNF4α (+) was significantly higher than those of the other three groups (P < 0.001). The OATP1B3 grade was also significantly higher in HCC with β-catenin/GS (+) HNF4α (+) (P < 0.001). Hepatocellular carcinoma with β-catenin/GS (+) HNF4α (+) showed the highest differentiation grade as compared to the other groups (P < 0.004). There were no significant differences in portal vein invasion, macroscopic growth pattern, or prognosis analyses between the four groups.
CONCLUSION
Co-activation of β-catenin and HNF4α would promote OATP1B3 expression, and consequently higher enhancement ratio on gadoxetic acid-enhanced MRI and higher differentiation grade in HCC.
目的
本研究旨在阐明β-连环蛋白与肝细胞核因子（HNF）4α的共激活与钆塞酸增强磁共振成像（MRI）表现、有机阴离子转运多肽（OATP）1B3表达以及肝细胞癌（HCC）组织学表现之间的相关性。
方法
本研究纳入了174例患者手术切除的196个HCC。根据β-连环蛋白、谷氨酰胺合成酶（GS）和HNF4α的免疫组化表达将HCC分为四组：（i）β-连环蛋白/GS（阳性[+]）HNF4α（+）；（ii）β-连环蛋白/GS（+）HNF4α（阴性[-]）；（iii）β-连环蛋白/GS（-）HNF4α（+）；（iv）β-连环蛋白/GS（-）HNF4α（-）。我们比较了四组在钆塞酸增强MRI肝胆期的增强率、免疫组化有机阴离子转运多肽（OATP）1B3（钆塞酸的主要摄取转运体）表达和组织学特征、总生存期和无复发生存期。采用Kruskal-Wallis检验、Steel-Dwass多重比较检验、Fisher精确检验和对数秩（Mantel-Cox）检验进行统计分析。
结果
β-连环蛋白/GS（+）HNF4α（+）的HCC在钆塞酸增强MRI上的增强率显著高于其他三组（P＜0.001）。β-连环蛋白/GS（+）HNF4α（+）的HCC中OATP1B3分级也显著更高（P＜0.001）。与其他组相比，β-连环蛋白/GS（+）HNF4α（+）的肝细胞癌分化程度最高（P＜0.004）。四组之间在门静脉侵犯、大体生长模式或预后分析方面无显著差异。
结论
β-连环蛋白和HNF4α的共激活会促进OATP1B3表达，从而使HCC在钆塞酸增强MRI上有更高的增强率和更高的分化程度。
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