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Overexpression of KIAA0101 Predicts High Stage, Early Tumor Recurrence, and Poor Prognosis of Hepatocellular Carcinoma

Authors' Affiliations: Departments of ¹ Surgery and ² Pathology and ³ National Center of Excellence for General Clinical Trial and Research, National Taiwan University Hospital; ⁴ Graduate Institute of Pathology and ⁵ Department of Surgery, College of Medicine and ⁶ College of Public Health, National Taiwan University, Taipei, Taiwan

Requests for reprints: Hey-Chi Hsu, Department of Pathology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan. Fax: 886-2-23410876; E-mail: heychi{at}ntu.edu.tw.

Purpose: KIAA0101 is a proliferating cell nuclear antigen–associated factor and involved in cell proliferation. This study is to elucidate its role in the progression, early tumor recurrence (ETR), and prognosis of hepatocellular carcinoma (HCC).

Experimental Design: KIAA0101 mRNA was measured by reverse transcription-PCR in 216 resected, unifocal, primary HCCs and its protein in 164 cases by immunohistochemistry.

Results: KIAA0101 mRNA was overexpressed in 131 (61%) HCCs, and protein was detected in 105 (64%). KIAA0101 mRNA overexpression correlated with higher tumor grade (P = 0.0001), higher tumor stage with vascular invasion and various extents of intrahepatic spread (P = 1 x 10^–8), ETR (P = 1.8 x 10^–6), and lower 5-year survival (P = 0.0026). Multivariate analysis confirmed that KIAA0101 overexpression was an independent risk factor associated with high-grade tumor (P = 0.0001), high-stage tumor (P < 0.0001), and ETR (P = 0.0052) and thus contributed to poor prognosis. KIAA0101 protein–positive tumor cells accumulated at the borders of tumor macrotrabeculae and were more abundant in tumor thrombi than in the main tumors. Hence, KIAA0101 may contribute to growth advantage and resistance to hypoxic insult. In this series, p53 mutation was detected in 93 of 184 (51%) HCCs. In both p53-mutated and non–p53-mutated HCCs, KIAA0101 overexpression correlated with higher vascular invasion (stages IIIA to IV; all Ps < 0.0001) and, accordingly, led to lower 5-year survival rates (P = 0.011 and 0.029, respectively).

Conclusion: KIAA0101 correlates with enhanced metastatic potential and is a significant prognostic factor of HCC.

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