Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

The Central Role of c-Myc during Malignant Conversion in Human Hepatocarcinogenesis

ABSTRACT: Hepatocarcinogenesis is a multi-stage process in which precursor lesions progress into early hepatocellular carcinomas (eHCC) by sequential accumulation of multiple genetic and epigenetic alterations. To decode the molecular events during early stages of liver carcinogenesis, we performed gene expression profiling on cirrhotic (regenerative) and dysplastic nodules (DN) as well as eHCC. Although considerable heterogeneity was observed at the regenerative and dysplastic stages, clear differences were detected between DN and eHCC which included 460 differentially expressed genes. Functional analysis of the significant gene set identified the MYC oncogene as a plausible driver gene for malignant conversion of the dysplastic nodules. In addition, gene set enrichment analysis (GSEA) revealed a remarkable enrichment of MYC up-regulated gene set in eHCC versus dysplasia. Presence of the MYC signature significantly correlated with increased expression of CSN5 as well as with the higher overall transcription rate of genes located in the 8q chromosome region. Furthermore, a classifier constructed from MYC target genes could robustly discriminate eHCC from high- and low-grade dysplastic nodules. In conclusion, our study identified unique expression patterns associated with the transition of high-grade dysplastic nodules to early HCC and demonstrated that activation of the MYC transcription signature is critical for the malignant conversion of pre-neoplastic liver lesions. Samples from forty-nine nodular liver lesions including 24 regenerative (cirrhotic) nodules (CN), 3 low-grade (LGDN), 12 high-grade dysplastic nodules (HGDN) and 10 early hepatocellular carcinomas (Early HCC) were used. The Human Operon V2 oligonucleotide library containing 22K features representing expressed sequences was printed to glass arrays in the Advanced Technology Center (National Cancer Institute, Gaithersburg, MD). The aRNA probes were fragmented and hybridized to the microarray slides following the standard procedures. All samples were hybridized against a common amplified reference RNA pooled from normal liver samples. Experimental duplicates were prepared following a reverse-flour design.

ORGANISM(S): Homo sapiens

SUBMITTER: Snorri Thorgeirsson

PROVIDER: E-GEOD-12443 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Central role of c-Myc during malignant conversion in human hepatocarcinogenesis.

Kaposi-Novak Pal P Libbrecht Louis L Woo Hyun Goo HG Lee Yun-Han YH Sears Nathaniel C NC Coulouarn Cedric C Conner Elizabeth A EA Factor Valentina M VM Roskams Tania T Thorgeirsson Snorri S SS

Cancer research 20090310 7

Hepatocarcinogenesis is a multistage process in which precursor lesions progress into early hepatocellular carcinomas (eHCC) by sequential accumulation of multiple genetic and epigenetic alterations. To decode the molecular events during early stages of liver carcinogenesis, we performed gene expression profiling on cirrhotic (regenerative) and dysplastic nodules (DN), as well as eHCC. Although considerable heterogeneity was observed at the regenerative and dysplastic stages, overall, 460 differ ...[more]

PMID: 19276364

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Dataset Information

The Central Role of c-Myc during Malignant Conversion in Human Hepatocarcinogenesis

Publications

Central role of c-Myc during malignant conversion in human hepatocarcinogenesis.

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