Overexpressed Id-1 is associated with a high risk of hepatocellular carcinoma development in patients with cirrhosis without transcriptional repression of p16
Overexpressed Id-1 is associated with a high risk of hepatocellular carcinoma development in patients with cirrhosis without transcriptional repression of p16
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DOI：
10.1002/cncr.21259
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发表时间：
2005-09-01
期刊：
影响因子：
6.2
通讯作者：
Aoyagi, Y
中科院分区：
文献类型：
--
作者：
Matsuda, Y;Yamagiwa, S;Aoyagi, Y
背景。分化抑制剂/DNA 结合蛋白 1 (Id-1) 通过抑制碱性螺旋-环-螺旋 (HLH) 转录因子，在细胞增殖和癌变调节中发挥关键作用。最近，发现 Id-1 在包括肝细胞癌 (HCC) 在内的肿瘤组织标本中抑制 p16，但其在癌前肝组织中的相关性尚不清楚。采用免疫组织化学方法研究了112例肝硬化非肝癌患者肝组织标本中Id-1的表达情况。研究了 Id-1 表达与临床病理特征、p16 状态以及 HCC 发生风险之间的相关性。结果。在 42 名患者 (38%) 中观察到 Id-1 高表达。 Id-1表达水平与临床标准参数或肝硬化组织标本中p16的状态无关。 Id-1 高表达组患者的 HCC 累积发生率显着较高（P < 0.0008）。多变量分析显示，Id-1表达增加是肝硬化患者发生HCC风险的独立显着因素（相对风险=2.75，P=0.003）。结论。本研究结果表明，Id-1表达增加可能在肝癌发生的早期阶段发挥重要作用，并可能作为确定肝硬化患者发生HCC高风险的有用标志物。
BACKGROUND. Inhibitor of differentiation/ DNA binding protein 1 (Id-1) plays a pivotal role in the regulation of cell proliferation and carcinogenesis via inhibiting basic helix-loop -helix (HLH) transcription factors. Recently, Id-1 was found to repress p16 in tumorous tissue specimens including hepatocellular carcinoma (HCC), but its relevance in precancerous liver tissues is unknown.METHODS. Id-1 expression in the liver tissue specimens of 112 patients with cirrhosis without HCC was studied by immunohistochemical analysis. Correlations were investigated between Id-1 expression and clinicopathologic features, the status of p16, and the risk of HCC occurrence.RESULTS. A high expression of Id-1 was observed in 42 patients (38%). The level of Id-1 expression was not associated with clinical standard parameters or the status of p16 in cirrhotic tissue specimens. The cumulative incidence of HCC development was significantly higher in a group of patients with high Id-1 expression (P 0.0008). Multivariate analysis revealed that increased Id-1 expression is an independent significant factor for the risk of HCC development in patients with cirrhosis (relative risk = 2.75, P = 0.003).CONCLUSIONS. The results of the current study suggested that increased expression of Id-1 may play an important role in the early step of hepatocarcinogenesis, and might serve as a useful marker for determining patients with cirrhosis with a high risk of HCC occurrence.