Increased expression of HOXB9 in hepatocellular carcinoma predicts poor overall survival but a beneficial response to sorafenib

Chiba,Naokazu; Ozawa,Yosuke; Hikita,Kosuke; Okihara,Masaaki; Sano,Toru; Tomita,Koichi; Takano,Kiminori; Kawachi,Shigeyuki

doi:10.3892/or.2017.5474

Increased expression of HOXB9 in hepatocellular carcinoma predicts poor overall survival but a beneficial response to sorafenib

Authors:
- Naokazu Chiba
- Yosuke Ozawa
- Kosuke Hikita
- Masaaki Okihara
- Toru Sano
- Koichi Tomita
- Kiminori Takano
- Shigeyuki Kawachi
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Affiliations: Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Tokyo 193-0998, Japan
Published online on: February 23, 2017 https://doi.org/10.3892/or.2017.5474
Pages: 2270-2276

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Abstract

At advanced stages of hepatocellular carcinoma (HCC), the multikinase inhibitor sorafenib is the only effective treatment. Surrogate markers that predict the biological and clinical efficacy of sorafenib may help tailor treatment on an individual patient basis. In the present study, the clinical significance of the expression of HOXB9, a transcriptional factor, in HCC was assessed. Increased HOXB9 expression in HCC was found to be positively correlated with the expression of angiogenic factors, increased vascular invasion and was found to be associated with poor overall patient survival. Sorafenib treatment effectively suppressed the expression of angiogenic factors and activation of the Raf/MEK/ERK pathway in HOXB9-expressing HCC cell lines. Consistent with these findings, HCC patients, whose cancer expressed high levels of HOXB9, exhibited increased overall survival upon sorafenib treatment. Collectively, these results suggest that HOXB9 expression in HCC could be a surrogate marker for a beneficial response to sorafenib treatment.

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