The Clinical Impact of Transcatheter Arterial Chemoembolization (TACE)-Induced c-Met Upregulation on TACE Refractoriness in Hepatocellular Carcinoma
The Clinical Impact of Transcatheter Arterial Chemoembolization (TACE)-Induced c-Met Upregulation on TACE Refractoriness in Hepatocellular Carcinoma
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DOI：
10.1007/s10620-015-4018-9
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发表时间：
2016-06-01
影响因子：
3.1
通讯作者：
Mori, Masaki
中科院分区：
文献类型：
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作者：
Kajihara, Jun;Tomimaru, Yoshito;Mori, Masaki
经导管动脉化疗栓塞术（TACE）是一种广泛应用且成熟的肝细胞癌（HCC）治疗方法。然而，TACE在反复进行时失去其治疗效果，这种现象称为TACE难治性。c-Met与某些类型癌症的恶性潜能和抗肿瘤治疗的抗性相关。本研究的目的是研究TACE对c-Met表达的临床影响，以了解TACE无效的机制。在体外研究了TACE对HCC细胞系c-Met表达水平的影响，并且显示在缺氧和/或暴露于化疗剂下培养的HCC细胞系中c-Met表达上调。使用82例接受和未接受术前TACE治疗的HCC临床样本验证体外结果。在接受术前TACE治疗的HCC临床样本中，c-Met上调的频率显著高于未接受TACE治疗的样本。c-Met表达增加与预后不良显著相关。TACE治疗后c-Met表达上调，c-Met表达上调可能是TACE治疗无效的原因之一。
Transcatheter arterial chemoembolization (TACE) is a widely used and well-established treatment for hepatocellular carcinoma (HCC). However, TACE loses its therapeutic efficacy when performed repeatedly, a phenomenon termed TACE refractoriness. c-Met is associated with malignant potential and with resistance to anti-tumor therapies in some kinds of cancers.The aim of this study is to investigate the clinical impact of TACE on c-Met expression with the aim of understanding the mechanism underlying TACE refractoriness.The effect of TACE on the c-Met expression level was investigated in vitro in HCC cell lines, and it was shown that c-Met expression is upregulated in HCC cell lines cultured under hypoxia and/or exposed to chemotherapeutic agents. The in vitro results were validated using 82 clinical samples of HCC with and without preoperative TACE treatment.c-Met upregulation was observed significantly more frequently in clinical samples of HCC that were treated with preoperative TACE than in samples with no TACE treatment. Increased c-Met expression was significantly associated with poor prognosis. Furthermore, the incidence of c-Met-positive expression was significantly higher in TACE-refractory HCC samples.TACE treatment upregulates c-Met expression in HCC and the upregulated c-Met expression may be responsible for TACE refractoriness.