Yuan Ray-Hwang, Jeng Yung-Ming, Pan Hung-Wei, Hu Fu-Chang, Lai Po-Lin, Lee Po-Huang, Hsu Hey-Chi
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5368-76. doi: 10.1158/1078-0432.CCR-07-1113.
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).
KIAA0101 mRNA was measured by reverse transcription-PCR in 216 resected, unifocal, primary HCCs and its protein in 164 cases by immunohistochemistry.
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 macro-trabeculae 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).
KIAA0101 correlates with enhanced metastatic potential and is a significant prognostic factor of HCC.
KIAA0101是一种增殖细胞核抗原相关因子，参与细胞增殖。本研究旨在阐明其在肝细胞癌（HCC）进展、早期肿瘤复发（ETR）及预后中的作用。
采用逆转录-聚合酶链反应（RT-PCR）检测216例手术切除的单发原发性肝癌组织中KIAA0101 mRNA的表达，采用免疫组织化学方法检测164例组织中KIAA0101蛋白的表达。
131例（61%）HCC中KIAA0101 mRNA过表达，105例（64%）检测到KIAA0101蛋白。KIAA0101 mRNA过表达与肿瘤分级较高（P = 0.0001）、伴有血管侵犯及不同程度肝内播散的肿瘤分期较高（P = 1×10⁻⁸）、ETR（P = 1.8×10⁻⁶）及5年生存率较低（P = 0.0026）相关。多因素分析证实，KIAA0101过表达是与高级别肿瘤（P = 0.0001）、高分期肿瘤（P < 0.0001）及ETR（P = 0.0052）相关的独立危险因素，因此提示预后不良。KIAA0101蛋白阳性肿瘤细胞聚集在肿瘤大条索边缘，在肿瘤血栓中比在主要肿瘤中更丰富。因此，KIAA0101可能有助于生长优势和对缺氧损伤的抵抗。在本系列研究中，184例HCC中有93例（51%）检测到p53突变。在p53突变和非p53突变的HCC中，KIAA0101过表达均与较高的血管侵犯相关（ⅢA至Ⅳ期；所有P < 0.0001），相应地导致较低的5年生存率（分别为P = 0.011和0.029）。
KIAA0101与转移潜能增强相关，是HCC的重要预后因素。
