TOP2A overexpression in hepatocellular carcinoma correlates with early age onset, shorter patients survival and chemoresistance
TOP2A overexpression in hepatocellular carcinoma correlates with early age onset, shorter patients survival and chemoresistance
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DOI：
10.1002/ijc.23968
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发表时间：
2009-02-01
影响因子：
6.4
通讯作者：
To, Ka-Fai
中科院分区：
文献类型：
--
作者：
Wong, Nathalie;Yen, Winnie;To, Ka-Fai
基因组增益是原癌基因激活的重要机制。在许多情况下，诱导癌基因作为预后标志物和治疗设计的靶标具有临床意义。在肝细胞癌（HCC）中，虽然染色体增加是常见的，但关于潜在癌基因诱导的信息仍然很少。在这里，我们通过基于阵列的转录作图检查了HCC的7个致病位点过度表达基因。在22个HCC细胞系和培养物的早期传代中，发现了上调基因簇，其中TOP2A表达最高。相对于邻近的非肿瘤肝脏，在独立的HCC肿瘤系列中证实了不同的TOP2A转录（p = 0.0018）。通过对172例HCC的组织芯片分析，我们发现TOP2A的表达与早期组织学分级（p < 0.001）、微血管侵袭（p = 0.004）和早期恶性肿瘤发病（p < 0.001）相关。
Genomic gain represents an important mechanism in the activation of proto-oncogenes. In many instances, induced oncogenes hold clinical implications both as prognostic markers and targets for therapeutic design. In hepatocellular carcinoma (HCC), although chromosomal gains are common, information on underlying oncogenes induced remains minimal. Here, we examined 7 causal sites of HCC for overexpressed genes by array-based transcriptional mapping. In 22 HCC cell lines and early passages of cultures studied, clusters of up-regulated genes were indicated, where TOP2A expression ranked the highest. Distinct TOP2A transcriptions were confirmed in an independent series of HCC tumors relative to adjacent non-tumoral liver (p = 0.0018). By tissue microarray analysis of 172 HCC, we found TOP2A expressions correlated with advance histological grading (p < 0.001), microvascular invasion (p = 0.004) and an early age onset of the malignancy (