演題抄録

FACO International Workshop

開催概要
開催回
第53回・2015年・京都
 

c-Met expression in HCC is a dominant target in TACE treatment

演題番号 : FWS4-2

[筆頭演者]
Yamada Daisaku:1 
[共同演者]
Eguchi Hidetoshi:1、Wada Hiroshi:1、Kajihara Jun:1、Asaoka Tadafumi:1、Noda Takehiro:1、Goto Kunihito:1、Tomimaru Yoshito:2、Doki Yuichiro:1、Mori Masaki:1

1:Gastroenterological surgery, Graduate School of Medicine, Osaka University、2:Department of surgery, Toyonaka Municipal Hospital

 

Background and Aims: There is no available effective systemic treatment for patients with advanced hepatocellular carcinoma (HCC) except for transarterial chemoembolization (TACE) or sorafenib treatment. c-Met expression in HCC was recently reported as a prognostic marker for overall survival (OS) of HCC including advanced stage, but the mechanisms contributing to the progression are still unclear. Our aims are to investigate the factors inducing c-Met expression, and to elucidate the role of the factors in the tumor development. Methods: Fresh HCC samples were obtained from 96 patients who underwent curative liver resection at Osaka university hospital. Immunohistochemistory for c-Met expression was performed on resected specimens, and c-Met expression was evaluated by the intensity of positive staining; >20% of tumor section was classified into c-Methigh group. Using HCC cell lines (HuH7 and PLC/PRF/5), the alteration of mRNA and cell viability were investigated under the stress; hypoxia and/or a chemotherapeutic drug (doxorubicin, DXR or cisplatin, CDDP). Results: OS in c-Methigh group was significantly shorter than that in c-Metlow group. From the comparison of each group, preoperative TACE treatment is an independent factor in c-Methigh group. Mimicking TACE, HCC cells were cultured under hypoxia, and treated with DXR or CDDP. c-Met mRNA expression was significantly increased by either stress. The patients in c-Methigh group became resistant to TACE earlier compared to c-Metlow group, indicating c-Met positive HCC cells are resistant to TACE. To investigate the role of c-Met, HCC cell lines were cultured in TACE situation with c-Met inhibitor, and c-Met inhibitor significantly decreased cell viability. Conclusion: TACE may induce c-Met positive cells in HCC, and c-Met positive HCC therefore became resistant to TACE. From our data, inhibition of c-Met will be a good treatment option for c-Met positive HCC patients, especially the patients with advanced HCC.

キーワード

臓器別:肝臓

手法別:トランスレーショナルリサーチ

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