A Meta-Analysis of Array-CGH Studies Implicates Antiviral Immunity Pathways in the Development of Hepatocellular Carcinoma
A Meta-Analysis of Array-CGH Studies Implicates Antiviral Immunity Pathways in the Development of Hepatocellular Carcinoma
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DOI：
10.1371/journal.pone.0028404
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发表时间：
2011-12-12
期刊：
影响因子：
3.7
通讯作者：
Xing, Jinliang
中科院分区：
文献类型：
--
作者：
Guo, Xu;Ba, Yanna;Xing, Jinliang
背景：肝细胞癌（HCC）的发生和进展与基因组改变的积累显着相关。基于阵列的比较基因组杂交（阵列 CGH）已应用于包括 HCC 在内的多种肿瘤，用于对 DNA 拷贝数变化进行全基因组高分辨率筛查。然而，在HCC发展中起核心作用的相关染色体变异仍未完全阐明。方法：在本研究中，为了进一步表征对HCC发展重要的拷贝数改变（CNA），我们对四个已发表的独立阵列-CGH数据集（包括总共159个样本）进行了荟萃分析。结果：85个显着增益（频率> = 25％）主要映射到五个广泛的染色体区域，包括1q， 6p、8q、17q 和 20p，以及两个狭窄区域 5p15.33 和 9q34.2-34.3。 88 个显着损失（频率 >= 25%）最常见于 4q、6q、8p、9p、13q、14q、16q 和 17p。位于同一染色体或不同染色体上的染色体畸变之间存在显着的相关性。具有不同病因的 HCC 在很大程度上表现出惊人相似的染色体畸变特征，只有少数例外。此外，京都基因和基因组百科全书 (KEGG) 通路分析表明，受这些染色体畸变影响的基因在 31 条经典通路中显着富集，其中在抗病毒免疫通路中观察到的富集度最高。结论：综上所述，我们的研究结果为抗病毒免疫相关基因通路在 HCC 发病机制和进展中的影响提供了新颖且重要的线索。
Background: The development and progression of hepatocellular carcinoma (HCC) is significantly correlated to the accumulation of genomic alterations. Array-based comparative genomic hybridization (array CGH) has been applied to a wide range of tumors including HCCs for the genome-wide high resolution screening of DNA copy number changes. However, the relevant chromosomal variations that play a central role in the development of HCC still are not fully elucidated.Methods: In present study, in order to further characterize the copy number alterations (CNAs) important to HCC development, we conducted a meta-analysis of four published independent array-CGH datasets including total 159 samples.Results: Eighty five significant gains (frequency >= 25%) were mostly mapped to five broad chromosomal regions including 1q, 6p, 8q, 17q and 20p, as well as two narrow regions 5p15.33 and 9q34.2-34.3. Eighty eight significant losses (frequency >= 25%) were most frequently present in 4q, 6q, 8p, 9p, 13q, 14q, 16q, and 17p. Significant correlations existed between chromosomal aberrations either located on the same chromosome or the different chromosomes. HCCs with different etiologies largely exhibited surprisingly similar profiles of chromosomal aberrations with only a few exceptions. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the genes affected by these chromosomal aberrations were significantly enriched in 31 canonical pathways with the highest enrichment observed for antiviral immunity pathways.Conclusions: Taken together, our findings provide novel and important clues for the implications of antiviral immunity-related gene pathways in the pathogenesis and progression of HCC.