Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma.
Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma.
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DOI：
10.1002/hep.27093
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发表时间：
2014-11
期刊：
影响因子：
13.5
通讯作者：
Kaneko, Shuichi
中科院分区：
文献类型：
--
作者：
Yamashita, Taro;Kitao, Azusa;Matsui, Osamu;Hayashi, Takehiro;Nio, Kouki;Kondo, Mitsumasa;Ohno, Naoki;Miyati, Tosiaki;Okada, Hikari;Yamashita, Tatsuya;Mizukoshi, Eishiro;Honda, Masao;Nakanuma, Yasuni;Takamura, Hiroyuki;Ohta, Tetsuo;Nakamoto, Yasunari;Yamamoto, Masakazu;Takayama, Tadatoshi;Arii, Shigeki;Wang, XinWei;Kaneko, Shuichi
肝细胞癌（HCC）患者的生存率通常是个体差异的，即使在早期肿瘤手术后也是如此。钆乙氧基苄基二亚乙基三胺五乙酸（Gd-EOB-DTPA）增强磁共振成像（MRI）最近已被引入，以评估肝脏病变的血管和活性的有机阴离子转运蛋白OATP 1B 3。在这里，我们报告Gd-EOB-DTPA增强MRI（EOB-MRI）结合血清甲胎蛋白（AFP）状态反映了HCC的干/成熟状态，具有独特的生物学和预后信息。在大约15%的HCC中观察到肝胆相的Gd-EOB-DTPA摄取。这种摄取与低血清AFP水平、通过上调OATP 1B 3和HNF 4A表达维持肝细胞功能以及良好预后相关。相比之下，肝癌显示Gd-EOB-DTPA摄取减少，血清AFP水平高，与预后差和癌基因FOXM 1的激活有关。在显示Gd-EOB-DTPA摄取的HCC细胞中敲低HNF 4A导致AFP和FOXM 1表达增加以及OATP 1B 3表达丧失，伴随着形态学改变、肿瘤发生增强以及体内Gd-EOB-DTPA摄取丧失。基于EOB-MRI和血清AFP水平的HCC分类预测单机构队列（n = 70）的总生存率，其预后效用在多机构早期HCC队列（n = 109）中独立验证。总结：这种非侵入性分类系统是基于HCC的干细胞/成熟状态的分子，可以纳入目前的分期实践，以改善管理算法，特别是在疾病的早期阶段。
The survival of patients with hepatocellular carcinoma (HCC) is often individually different even after surgery for early-stage tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) has been introduced recently to evaluate hepatic lesions with regard to vascularity and the activity of the organic anion transporter OATP1B3. Here, we report that Gd-EOB-DTPA-enhanced MRI (EOB-MRI) in combination with serum alpha-fetoprotein (AFP) status reflects the stem/maturational status of HCC with distinct biology and prognostic information. Gd-EOB-DTPA uptake in the hepatobiliary phase was observed in approximately 15% of HCCs. This uptake correlated with low serum AFP levels, maintenance of hepatocyte function with the up-regulation of OATP1B3 and HNF4A expression, and good prognosis. By contrast, HCC showing reduced Gd-EOB-DTPA uptake with high serum AFP levels was associated with poor prognosis and the activation of the oncogene FOXM1. Knockdown of HNF4A in HCC cells showing Gd-EOB-DTPA uptake resulted in the increased expression of AFP and FOXM1 and the loss of OATP1B3 expression accompanied by morphological changes, enhanced tumorigenesis, and loss of Gd-EOB-DTPA uptake in vivo. HCC classification based on EOB-MRI and serum AFP levels predicted overall survival in a single-institution cohort (n = 70), and its prognostic utility was validated independently in a multi-institution cohort of early-stage HCCs (n = 109). Conclusion: This non-invasive classification system is molecularly based on the stem/maturation status of HCCs and can be incorporated into current staging practices to improve management algorithms, especially in the early stage of disease.
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影响因子：
11.2
作者：
Raychaudhuri P;Park HJ
通讯作者：
Park HJ
影响因子：
64.5
作者：
Hatziapostolou M;Polytarchou C;Aggelidou E;Drakaki A;Poultsides GA;Jaeger SA;Ogata H;Karin M;Struhl K;Hadzopoulou-Cladaras M;Iliopoulos D
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Iliopoulos D
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作者：
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Peng, Zhihai
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作者：
Crestani, M;De Fabiani, E;Galli, G
通讯作者：
Galli, G
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作者：
Llovet, Josep M.;Chen, Yingbei;Friedman, Scott L.
通讯作者：
Friedman, Scott L.