A tumor progression model for hepatocellular carcinoma: Bioinformatic analysis of genomic data
A tumor progression model for hepatocellular carcinoma: Bioinformatic analysis of genomic data
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DOI：
10.1053/j.gastro.2006.08.014
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发表时间：
2006-10-01
期刊：
影响因子：
29.4
通讯作者：
Sung, Joseph J. Y.
中科院分区：
文献类型：
--
作者：
Poon, Terence C. W.;Wong, Nathalie;Sung, Joseph J. Y.
背景与目的：基因组异常是人类癌症发生的基础，这一点已被广泛认识。染色体变化的异常模式可能代表有用的信息，可用于对肝癌病例的复杂性状进行分类，以确定肿瘤癌变、肿瘤进展和预后中涉及的遗传事件。研究方法：应用比较基因组杂交（CGH）技术研究了158例乙型肝炎病毒（B）相关性肝细胞癌（HCC）的染色体畸变。通过应用自组织树算法，统计学显著的CGH事件被用于构建进化树，该进化树可以推断具有不同程度的肿瘤进展的患者亚组。确定了亚组中的关键CGH事件。检查了分组和关键CGH事件的临床意义。结果：根据显著染色体畸变的模式，在进化树中确定了3个HCC亚组。分组具有反映肿瘤进展程度的信息，包括染色体畸变数量、肿瘤分期、肿瘤大小和疾病结局。1 q21 -23和8 q22 -24的增加被确定为与HCC早期发展相关的基因组事件。然而，3q 22 -24的增加被确定为发现与肿瘤复发和患者总体生存率差相关的晚期基因组事件之一。结论：构建了HCC的肿瘤进展模型，并揭示了与该疾病的临床病理特征显著相关的染色体不平衡。该模型解释了HCC患者临床结局的显著差异。
Background & Aims: it is widely recognized that genomic abnormalities underpin the development of human cancers. Aberrant patterns of chromosomal changes may represent useful information that can be used in classifying the complex traits of liver cancer cases for the genetic events involved in tumor carcinogenesis, tumor progression, and prognosis. Methods: Genome-wide chromosomal aberrations of 158 hepatitis B virus-associated hepatocellular carcinoma (HCC) were studied by comparative genomic hybridization (CGH). By application of a self-organizing tree algorithm, statistically significant CGH events were used to construct an evolutionary tree that could infer patient subgroups with different degrees of tumor progression. The key CGH events in the subgroups were identified. The clinical significance of the groupings and the key CGH events were examined. Results: Based on the patterns of significant chromosomal aberrations derived, 3 HCC subgroups organized in an evolutionary tree were identified. The groupings possessed information reflecting the degrees of tumor progression, including numbers of chromosomal aberrations, tumor stages, tumor sizes, and disease outcome. Gains of 1q21-23 and 8q22-24 were identified as genomic events associated with the early development of HCC. Gain of 3q22-24, however, was identified as 1 of the late genomic events found to be associated with tumor recurrence and poor overall patient survival. Conclusions: A tumor progression model for HCC was constructed and revealed chromosomal imbalances that were significantly associated with clinical pathologic characteristics of the disease. This model explains a significant part of the variations in clinical outcome among HCC patients.