Abstract 3290: Overexpression of Aurora B kinase is correlated with vascular invasion and metastasis of human hepatocellular carcinoma

Abstract

Abstract Background: We previously demonstrated that Aurora B overexpression correlated well with higher histology grade and more advanced stage of hepatocellular carcinoma (HCC). In this study, we sought to analyze the association between Aurora B overexpression and vascular invasion/metastasis of HCC, as well as the potential of AZD1152, a novel and selective Aurora B kinase inhibitor in preventing vascular invasion and metastasis of HCC. Method: Aurora B mRNA levels were measured in HCC and paired non-tumorous liver tissues by reverse transcription-PCR. One hundred and sixty surgically resected, primary unifocal HCCs were selected for this study. Vascular invasion was determined by pathologic examination. All 160 patients had been followed for more than 5 years or until death. Forty-nine patients developed extrahepatic tumor metastasis. Multivariate analysis was conducted to determine the significance of Aurora B overexpression on vascular invasion and metastasis of HCC. The effects of AZD1152 on tumor invasiveness were tested in Huh-7 and HA-27T HCC cell lines by migration and invasion assays. Results: Overexpression of Aurora B was found in 98 of the 160 (61%) primary HCC. Univariate analysis showed that vascular invasion and metastasis were both associated with younger age (≤ 55 years, P = 0.027 and P = 0.003, respectively), high α-fetoprotein levels (> 200 ng/mL, P < 0.001 and P = 0.008), large tumor size (> 5 cm, P < 0.001 and P < 0.001), higher tumor grade (grade III-IV, P < 0.001 and P = 0.025), as well as Aurora B overexpression (P < 0.001 and P < 0.001). Multivariate analysis confirmed that Aurora B overexpression was an independent risk factor associated with vascular invasion (odds ratio, 2.659; P = 0.0183) and metastasis (odds ratio, 4.195; P = 0.0027). AZD1152, 5-125 nM, induced dose-dependent inhibition on migration and invasion in Huh-7 and HA-27T cells. Conclusions: Overexpression of Aurora B correlates well with vascular invasion and metastasis of HCC. Inhibition of Aurora B kinase by small molecular inhibitors may suppress invasion and metastasis of HCC. Grant support: Grant NSC96-2628-B-002-054-MY3 from the National Science Council (Taiwan), Grant DOH97-TD-B-111-001 from the Department of Health (Taiwan), and Grant NSC98-3112-B-075A-001 from the National Science Council (Taiwan). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3290.