Identification of novel tumor markers in hepatitis C virus-associated hepatocellular carcinoma.
Identification of novel tumor markers in hepatitis C virus-associated hepatocellular carcinoma.
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发表时间：
2003-02
期刊：
影响因子：
11.2
通讯作者：
Maria W. Smith;Zhaoxia N Yue;G. Geiss;Natalya Y. Sadovnikova;V. Carter;L. Boix;C. Lázaro;G. B. Rosenberg;Roger E Bumgarner;N. Fausto;J. Bruix;M. Katze
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作者：
Maria W. Smith;Zhaoxia N Yue;G. Geiss;Natalya Y. Sadovnikova;V. Carter;L. Boix;C. Lázaro;G. B. Rosenberg;Roger E Bumgarner;N. Fausto;J. Bruix;M. Katze
肝细胞癌（HCC）是一种常见的原发性恶性肿瘤，常与丙型肝炎病毒（HCV）相关.为了深入了解肝癌发生的分子机制，并确定潜在的HCC标志物，我们对20例HCV感染患者的手术肝脏样本进行了cDNA微阵列分析。将来自单个肿瘤的RNA与从所有病例中均为恶性的邻近非肿瘤组织中分离的RNA进行比较。与肝硬化相关的基因表达变化通过实验过滤掉，在实验中，将来自HCV感染的无肿瘤肝硬化的合并RNA与来自正常肝的合并RNA进行比较。使用Rosetta Resolver系统的高级分析工具分析了大约13，600个基因的表达。该分析揭示了一组50个潜在的HCC标志物基因，其在所分析的大多数肿瘤中上调，比常见的临床标志物如细胞增殖相关基因广泛得多。该HCC标志物集包含几个癌症相关基因，包括丝氨酸/苏氨酸激酶15（STK 15），其与染色体分离异常有关，但以前与肝癌无关。此外，还鉴定了一组编码分泌或血浆蛋白的基因，包括血浆谷氨酸羧肽酶（PGCP）和两种分泌型磷脂酶A2（PLA 2G 13和PLA 2G 7）。这些基因可能提供潜在的HCC血清学标志物，因为它们在超过一半的分析肿瘤中强烈上调。因此，高通量的方法加上高阶统计分析可能会导致发展新的诊断工具，肝脏恶性肿瘤。
Hepatocellular carcinoma (HCC) is a common primary cancer associated frequently with hepatitis C virus (HCV). To gain insight into the molecular mechanisms of hepatocarcinogenesis, and to identify potential HCC markers, we performed cDNA microarray analysis on surgical liver samples from 20 HCV-infected patients. RNA from individual tumors was compared with RNA isolated from adjacent nontumor tissue that was cirrhotic in all of the cases. Gene expression changes related to cirrhosis were filtered out using experiments in which pooled RNA from HCV-infected cirrhotic liver without tumors was compared with pooled RNA from normal liver. Expression of approximately 13,600 genes was analyzed using the advanced analysis tools of the Rosetta Resolver System. This analysis revealed a set of 50 potential HCC marker genes, which were up-regulated in the majority of the tumors analyzed, much more widely than common clinical markers such as cell proliferation-related genes. This HCC marker set contained several cancer-related genes, including serine/threonine kinase 15 (STK15), which has been implicated in chromosome segregation abnormalities but which has not been linked previously with liver cancer. In addition, a set of genes encoding secreted or plasma proteins was identified, including plasma glutamate carboxypeptidase (PGCP) and two secreted phospholipases A2 (PLA2G13 and PLA2G7). These genes may provide potential HCC serological markers because of their strong up-regulation in more than half of the tumors analyzed. Thus, high throughput methods coupled with high-order statistical analyses may result in the development of new diagnostic tools for liver malignancies.