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Molecular Signatures of Recurrent Hepatocellular Carcinoma Secondary to Hepatitis C Virus following Liver Transplantation.

Das T, Diamond DL, Yeh M, Hassan S, Bryan JT, Reyes JD, Perkins JD - J Transplant (2013)

Bottom Line: Gene expression profiling revealed 194 differentially regulated genes between the two groups.These genes belonged to cellular networks including cell cycle G1/S checkpoint regulators, RAN signaling, chronic myeloid leukemia signaling, molecular mechanisms of cancer, FXR/RXR activation and hepatic cholestasis.The expression levels of these genes were validated by quantitative PCR analysis.

View Article: PubMed Central - PubMed

Affiliation: Division of Transplantation, Department of Surgery, University of Washington School of Medicine, Seattle, WA 98195-6410, USA.

ABSTRACT
Chronic hepatitis C virus (HCV) induced hepatocellular carcinoma (HCC) is a primary indication for liver transplantation (LT). In western countries, the estimated rate of HCC recurrence following LT is between 15% and 20% and is a major cause of mortality. Currently, there is no standard method to treat patients who are at high risk for HCC recurrence. The aim of this study was to investigate the molecular signatures underlying HCC recurrence that may lead to future studies on gene regulation contributing to new therapeutic options. Two groups of patients were selected, one including patients with HCV who developed HCC recurrence (HCC-R) ≤3 years from LT and the second group including patients with HCV who did not have recurrent HCC (HCC-NR). Microarray analysis containing more than 29,000 known genes was performed on formalin-fixed-paraffin-embedded (FFPE) liver tissue from explanted livers. Gene expression profiling revealed 194 differentially regulated genes between the two groups. These genes belonged to cellular networks including cell cycle G1/S checkpoint regulators, RAN signaling, chronic myeloid leukemia signaling, molecular mechanisms of cancer, FXR/RXR activation and hepatic cholestasis. A subset of molecular signatures associated with HCC recurrence was found. The expression levels of these genes were validated by quantitative PCR analysis.

No MeSH data available.


Related in: MedlinePlus

Hierarchical clustering for 194 genes differentially expressed in HCC-R (FDR corrected ≤0.05). For visual comparison, genes differentially expressed in HCC-R and HCC-NR were clustered by the TreeView program. The red color represents genes upregulated, and the green color represents genes downregulated. Saturation was set at ±2-fold change.
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fig3: Hierarchical clustering for 194 genes differentially expressed in HCC-R (FDR corrected ≤0.05). For visual comparison, genes differentially expressed in HCC-R and HCC-NR were clustered by the TreeView program. The red color represents genes upregulated, and the green color represents genes downregulated. Saturation was set at ±2-fold change.

Mentions: The comparative transcriptome analyses aimed at identifying molecular signatures representative of HCC recurrence were carried out as described in Figure 2. Hierarchical clustering by gene expression segregated all HCC-R from HCC-NR. A total of 194 genes were identified to be differentially expressed, with 151 genes upregulated and 43 downregulated in HCC-R (Figure 3).


Molecular Signatures of Recurrent Hepatocellular Carcinoma Secondary to Hepatitis C Virus following Liver Transplantation.

Das T, Diamond DL, Yeh M, Hassan S, Bryan JT, Reyes JD, Perkins JD - J Transplant (2013)

Hierarchical clustering for 194 genes differentially expressed in HCC-R (FDR corrected ≤0.05). For visual comparison, genes differentially expressed in HCC-R and HCC-NR were clustered by the TreeView program. The red color represents genes upregulated, and the green color represents genes downregulated. Saturation was set at ±2-fold change.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3860124&req=5

fig3: Hierarchical clustering for 194 genes differentially expressed in HCC-R (FDR corrected ≤0.05). For visual comparison, genes differentially expressed in HCC-R and HCC-NR were clustered by the TreeView program. The red color represents genes upregulated, and the green color represents genes downregulated. Saturation was set at ±2-fold change.
Mentions: The comparative transcriptome analyses aimed at identifying molecular signatures representative of HCC recurrence were carried out as described in Figure 2. Hierarchical clustering by gene expression segregated all HCC-R from HCC-NR. A total of 194 genes were identified to be differentially expressed, with 151 genes upregulated and 43 downregulated in HCC-R (Figure 3).

Bottom Line: Gene expression profiling revealed 194 differentially regulated genes between the two groups.These genes belonged to cellular networks including cell cycle G1/S checkpoint regulators, RAN signaling, chronic myeloid leukemia signaling, molecular mechanisms of cancer, FXR/RXR activation and hepatic cholestasis.The expression levels of these genes were validated by quantitative PCR analysis.

View Article: PubMed Central - PubMed

Affiliation: Division of Transplantation, Department of Surgery, University of Washington School of Medicine, Seattle, WA 98195-6410, USA.

ABSTRACT
Chronic hepatitis C virus (HCV) induced hepatocellular carcinoma (HCC) is a primary indication for liver transplantation (LT). In western countries, the estimated rate of HCC recurrence following LT is between 15% and 20% and is a major cause of mortality. Currently, there is no standard method to treat patients who are at high risk for HCC recurrence. The aim of this study was to investigate the molecular signatures underlying HCC recurrence that may lead to future studies on gene regulation contributing to new therapeutic options. Two groups of patients were selected, one including patients with HCV who developed HCC recurrence (HCC-R) ≤3 years from LT and the second group including patients with HCV who did not have recurrent HCC (HCC-NR). Microarray analysis containing more than 29,000 known genes was performed on formalin-fixed-paraffin-embedded (FFPE) liver tissue from explanted livers. Gene expression profiling revealed 194 differentially regulated genes between the two groups. These genes belonged to cellular networks including cell cycle G1/S checkpoint regulators, RAN signaling, chronic myeloid leukemia signaling, molecular mechanisms of cancer, FXR/RXR activation and hepatic cholestasis. A subset of molecular signatures associated with HCC recurrence was found. The expression levels of these genes were validated by quantitative PCR analysis.

No MeSH data available.


Related in: MedlinePlus