Limits...
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

Network analysis of directly related genes which are upregulated and downregulated in HCC-R tumor tissues compared with HCC-NR tumor tissues. (a) The upregulated network includes genes dominated by regulators of cell cycle progression, cell growth and proliferation, DNA recombination, and cell-to-cell signaling genes. These are represented as respective shapes based on functional property in HCC-R tumor tissues. (b) The downregulated network includes genes reflecting the concurrent downregulation of genes related to innate immune response, cell-to-cell signaling, cell morphology, and cellular metabolism genes. These are represented as respective shapes based on their functional properties in HCC-R tumor tissues. The gray outlined nodules without expression are linker genes that are not altered in HCC-R but are statistically enriched for interaction with the altered genes.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3860124&req=5

fig4: Network analysis of directly related genes which are upregulated and downregulated in HCC-R tumor tissues compared with HCC-NR tumor tissues. (a) The upregulated network includes genes dominated by regulators of cell cycle progression, cell growth and proliferation, DNA recombination, and cell-to-cell signaling genes. These are represented as respective shapes based on functional property in HCC-R tumor tissues. (b) The downregulated network includes genes reflecting the concurrent downregulation of genes related to innate immune response, cell-to-cell signaling, cell morphology, and cellular metabolism genes. These are represented as respective shapes based on their functional properties in HCC-R tumor tissues. The gray outlined nodules without expression are linker genes that are not altered in HCC-R but are statistically enriched for interaction with the altered genes.

Mentions: Interestingly, when network analysis was performed, which allows exploration of the biological relationship between any two genes, it was seen that the largest number of genes with higher expression in HCC-R tumor tissue was dominated by major transcriptional regulators. These genes are associated with cellular malignancies by controlling cell cycle progression, cell growth and proliferation, cell-to-cell signaling, and cell survival and death. Additionally, a novel set of highly significant genes associated with tumor recurrence was identified (Figure 4(a)).


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)

Network analysis of directly related genes which are upregulated and downregulated in HCC-R tumor tissues compared with HCC-NR tumor tissues. (a) The upregulated network includes genes dominated by regulators of cell cycle progression, cell growth and proliferation, DNA recombination, and cell-to-cell signaling genes. These are represented as respective shapes based on functional property in HCC-R tumor tissues. (b) The downregulated network includes genes reflecting the concurrent downregulation of genes related to innate immune response, cell-to-cell signaling, cell morphology, and cellular metabolism genes. These are represented as respective shapes based on their functional properties in HCC-R tumor tissues. The gray outlined nodules without expression are linker genes that are not altered in HCC-R but are statistically enriched for interaction with the altered genes.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3860124&req=5

fig4: Network analysis of directly related genes which are upregulated and downregulated in HCC-R tumor tissues compared with HCC-NR tumor tissues. (a) The upregulated network includes genes dominated by regulators of cell cycle progression, cell growth and proliferation, DNA recombination, and cell-to-cell signaling genes. These are represented as respective shapes based on functional property in HCC-R tumor tissues. (b) The downregulated network includes genes reflecting the concurrent downregulation of genes related to innate immune response, cell-to-cell signaling, cell morphology, and cellular metabolism genes. These are represented as respective shapes based on their functional properties in HCC-R tumor tissues. The gray outlined nodules without expression are linker genes that are not altered in HCC-R but are statistically enriched for interaction with the altered genes.
Mentions: Interestingly, when network analysis was performed, which allows exploration of the biological relationship between any two genes, it was seen that the largest number of genes with higher expression in HCC-R tumor tissue was dominated by major transcriptional regulators. These genes are associated with cellular malignancies by controlling cell cycle progression, cell growth and proliferation, cell-to-cell signaling, and cell survival and death. Additionally, a novel set of highly significant genes associated with tumor recurrence was identified (Figure 4(a)).

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