title: Increased expression of HOXB9 in hepatocellular carcinoma predicts poor overall survival but a beneficial response to sorafenib.
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.
authors.affiliation: Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Tokyo 193-0998, Japan.
authors.forename: Naokazu
authors.initials: N
authors.lastname: Chiba
authors.affiliation: Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Tokyo 193-0998, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ozawa
authors.affiliation: Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Tokyo 193-0998, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Hikita
authors.affiliation: Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Tokyo 193-0998, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Okihara
authors.affiliation: Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Tokyo 193-0998, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Sano
authors.affiliation: Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Tokyo 193-0998, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Tomita
authors.affiliation: Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Tokyo 193-0998, Japan.
authors.forename: Kiminori
authors.initials: K
authors.lastname: Takano
authors.affiliation: Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Tokyo 193-0998, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kawachi
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008297:Male; D009361:Neoplasm Invasiveness; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D000077157:Sorafenib; D016019:Survival Analysis; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D043925:Angiogenesis Inducing Agents; C491257:HOXB9 protein, human; D018398:Homeodomain Proteins; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib