The Clinical Impact of Transcatheter Arterial Chemoembolization (TACE)-Induced c-Met Upregulation on TACE Refractoriness in Hepatocellular Carcinoma

Jun Kajihara, Yoshito Tomimaru, Hidetoshi Eguchi, Daisaku Yamada, Hiroshi Wada, Akira Tomokuni, Tadafumi Asaoka, Koichi Kawamoto, Shigeru Marubashi, Hiroaki Nagano, Koji Umeshita, Yuichiro Doki, Masaki Mori

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Abstract

Background: 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. Aims: 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. Methods: 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. Results: 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. Conclusions: TACE treatment upregulates c-Met expression in HCC and the upregulated c-Met expression may be responsible for TACE refractoriness.

Original languageEnglish
Pages (from-to)1572-1581
Number of pages10
JournalDigestive Diseases and Sciences
Volume61
Issue number6
DOIs
Publication statusPublished - Jun 1 2016

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Gastroenterology

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