A Meta-Analysis of Array-CGH Studies Implicates Antiviral Immunity Pathways in the Development of Hepatocellular Carcinoma

Abstract

BackgroundThe 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.MethodsIn 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.ResultsEighty 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.ConclusionsTaken together, our findings provide novel and important clues for the implications of antiviral immunity-related gene pathways in the pathogenesis and progression of HCC.

Genomic losses at 5q13.2 and 8p23.1 in dysplastic hepatocytes are common events in hepatitis B virus-related hepatocellular carcinoma

“…Using array CGH analysis from four studies, it was revealed that loci with genomic gains with a prevalence of >25% included 1q, 6p, 8q, 17q, 20p, 5p15.33 and 9q34. 2-34.3, and loci with genomic loss with prevalence of >25% comprised 4q, 6q, 8p, 9p, 13q, 14q, 16q and 17p, and were associated with 31 classical molecular pathways, particularly the antivirus immunological pathway (6).…”

Immortalization of epithelial cells in oral carcinogenesis as revealed by genome‐wide array comparative genomic hybridization: A meta‐analysis

“…Meta‐analysis is a systematic and quantitative analytical method that can be used to summarize and cross‐analyze the significance of results from multiple studies on the same disease . To date, only a few meta‐analysis studies have been conducted using assay CGH data . A critical prerequisite for this analysis was the requirement to standardize data of previously published CNAs through cross‐platform analysis.…”

Recent updates of genetic and genomic alterations in hepatocellular carcinoma

“…In one meta-analysis, using conventional CGH analysis with low resolution (approximately 2 Mb) from several studies, it was revealed that the most prominent changes were gains of 1q (57.1%), 8q (46.6%), 6p (23.3%), and 17q (22.2%); and losses of 8p (38%), 16q (35.9%), 4q (34.3%), 17p (32.1%), and 13q (26.2%). [25] Using array CGH analysis from four studies, it was revealed that loci with genomic gains with a prevalence of more than 25% included 1q, 6p, 8q, 17q, 20p, 5p15.33, and 9q34.2-34.3; and loci with genomic losses with prevalence of more than 25% comprised 4q, 6q, 8p, 9p, 13q, 14q, 16q, and 17p; and were associated with 31 classical molecular pathways, particularly the antivirus immunological pathway. [25] A series of tumor suppressor genes have been identified in these regions, such as PR domain containing 5 (PRDM5, 4q26), TP53 (17p13.1), retinoblastoma 1 (RB1, 13q14), and cadherin 1, type 1 (CDH1, 16q22.1).…”

“…[25] A series of tumor suppressor genes have been identified in these regions, such as PR domain containing 5 (PRDM5, 4q26), TP53 (17p13.1), retinoblastoma 1 (RB1, 13q14), and cadherin 1, type 1 (CDH1, 16q22.1). [26][27][28] Some clinicopathological associations have been noted with specific abnormalities: Losses of 4q, 13q, and 16q are associated with HBV infection, [25] loss of 4q has been associated with elevated α-fetoprotein levels, TP53 mutations, [29] tumor size, and vascular invasion [30] while 9p and 6q losses have been reported to be independent predictors of poor outcome of HCC patients, [31] and that losses of 4q, 13q, and 16q are associated with HBV infection.…”