Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Mouse Hepatocellular Carcinoma Study

ABSTRACT: Genetically modified mice have been extensively used for analyzing the molecular events that occur during the tumor development. However, in many cases, if not all, it is uncertain to what extent the mouse models reproduce features observed in the corresponding human conditions. This is due largely to lack of precise methods for direct and comprehensive comparison at the molecular level of the mouse and human tumors. We used global gene expression patterns of 68 hepatocellular carcinoma (HCC) from 7 different mouse models and 91 human HCC from pre-defined subclasses to obtain direct comparison of the molecular features of mouse and human HCC. Total RNAs were isolated from frozen liver tissue using CsCl density gradient centrifugation methods. Total RNA from the livers of 10 wild type mice were pooled and used as reference in entire microarray experiments. To obtain gene expression profile data from four transgenic HCC mouse models, 20 Î¼g of total RNAs from tissues were used to drive fluorescently (Cy-5 or Cy-3) labeled cDNA. At least two hybridizations were carried out for each tissue using dye-swap strategy to eliminate dye labeling bias.

ORGANISM(S): Mus musculus

SUBMITTER: D Calvisi

PROVIDER: E-GEOD-1897 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells.

Lee Ju-Seog JS Heo Jeonghoon J Libbrecht Louis L Chu In-Sun IS Kaposi-Novak Pal P Calvisi Diego F DF Mikaelyan Arsen A Roberts Lewis R LR Demetris Anthony J AJ Sun Zongtang Z Nevens Frederik F Roskams Tania T Thorgeirsson Snorri S SS

Nature medicine 20060312 4

The variability in the prognosis of individuals with hepatocellular carcinoma (HCC) suggests that HCC may comprise several distinct biological phenotypes. These phenotypes may result from activation of different oncogenic pathways during tumorigenesis and/or from a different cell of origin. Here we address whether the transcriptional characteristics of HCC can provide insight into the cellular origin of the tumor. We integrated gene expression data from rat fetal hepatoblasts and adult hepatocyt ...[more]

PMID: 16532004

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Project description: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.

Dataset Information

Mouse Hepatocellular Carcinoma Study

Publications

A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells.

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