title: High-level expression of HOXB13 is closely associated with tumor angiogenesis and poor prognosis of hepatocellular carcinoma.
abstract: Homeobox B13 (HOXB13) is generally considered as a crucial regulator of terminal cellular differentiation. More recently, the absent or aberrant expression of HOXB13 has been increasingly implicated in cancer development and metastasis. However, the expression of HOXB13 in hepatocellular carcinoma (HCC) and its correlation with tumor angiogenesis and prognosis still remain unclear. The aim of the study was to evaluate the expression of HOXB13 in patients with HCC and explore the relationship of HOXB13 expression with clinicopathologic factors, tumor angiogenesis and prognosis. Immunohistochemistry was performed to determine the expression of HOXB13 in HCC and corresponding paracarcinomatous tissues from 72 patients. Vascular endothelial growth factor (VEGF) and CD31 were only examined in tissues of HCC patients mentioned above. The results showed that HOXB13 expression was significantly (P <0.001) higher in HCC (69.4%) than that in surrounding non-tumor tissues (26.4%), positively correlated with tumor VEGF (P <0.001) and microvessel density (MVD) (P = 0.013). Besides, it was associated with tumor capsula (P <0.001), vascular invasion (P <0.001), Edmondson grade (P <0.001), AFP (P = 0.007) and TNM stage (P <0.001). Univariate analysis showed poorer overall survival (OS) rate and disease free survival (DFS) rate in patients expressing higher levels of HOXB13. HOXB13 was also found to be an independent poor prognostic factor of OS and DFS in multivariate analysis. Taken together, our results suggest that increased HOXB13 expression is associated with tumor angiogenesis and progression in HCC and may function as a promising biomarker for unfavorable prognosis of HCC.
authors.affiliation: Department of Hepatic Surgery, Anhui Provincial Hospital, Anhui Medical University Hefei 230001, P. R. China.
authors.forename: Jian-Yu
authors.initials: JY
authors.lastname: Zhu
authors.affiliation: Department of Hepatic Surgery, Anhui Provincial Hospital, Anhui Medical University Hefei 230001, P. R. China.
authors.forename: Qi-Kai
authors.initials: QK
authors.lastname: Sun
authors.affiliation: Department of Medical Oncology, Anhui Provincial Hospital, Anhui Medical University Hefei 230001, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Hepatic Surgery, Anhui Provincial Hospital, Anhui Medical University Hefei 230001, P. R. China ; Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery Hefei 230001, PR. China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Jia
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C484414:HOXB13 protein, human; D018398:Homeodomain Proteins
keywords: HOXB13; angiogenesis; biomarker; expression; hepatocellular carcinoma; prognosis