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Biomarkers of disease differentiation: HCV recurrence versus acute cellular rejection.

Gehrau R, Mas V, Archer K, Maluf D - Fibrogenesis Tissue Repair (2012)

Bottom Line: Liver Transplantation (LT) is the optimal surgical treatment for HCV-cirrhotic patients at end-stage liver disease.The accurate differential diagnosis between both conditions is critical for treatment choice, and similar histological features represent a challenge for pathologists.Whole-genome gene expression (WGE) analyses through well-defined oligonucleotide microarray platforms represent a powerful tool for the molecular characterization of biological process.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Virginia, Department of Surgery, Transplant Division, P.O. Box 800625, 904 Lane Rd, Charlottesville, VA, 22908-0625, USA.

ABSTRACT
The wound-healing process induced by chronic hepatitis C virus (HCV) infection triggers liver damage characterized by fibrosis development and finally cirrhosis. Liver Transplantation (LT) is the optimal surgical treatment for HCV-cirrhotic patients at end-stage liver disease. However, acute cellular rejection (ACR) and HCV recurrence disease represent two devastating complications post-LT. The accurate differential diagnosis between both conditions is critical for treatment choice, and similar histological features represent a challenge for pathologists. Moreover, the HCV recurrence disease severity is highly variable post-LT. HCV recurrence disease progression is characterized by an accelerated fibrogenesis process, and almost 30% of those patients develop cirrhosis at 5-years of follow-up. Whole-genome gene expression (WGE) analyses through well-defined oligonucleotide microarray platforms represent a powerful tool for the molecular characterization of biological process. In the present manuscript, the utility of microarray technology is applied for the ACR and HCV-recurrence biological characterization in post-LT liver biopsy samples. Moreover, WGE analysis was performed to identify predictive biomarkers of HCV recurrence severity in formalin-fixed paraffin-embedded liver biopsies prospectively collected.

No MeSH data available.


Related in: MedlinePlus

Molecular characterization of HCV-infected liver biopsy samples diagnosed with ACR or HCV recurrence. A. Venn diagram illustrating a total of 3747 differentially expressed probesets in three pairwise comparisons composed by HCV-ACR (acute cellular rejection in HCV infected patients), HCV recurrence, and chronic HCV liver biopsy samples. B. Heatmap and dendrogram resulting from agglomerative hierarchical clustering using Ward's method, using 1-Pearson's correlation for distance measure.
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Figure 2: Molecular characterization of HCV-infected liver biopsy samples diagnosed with ACR or HCV recurrence. A. Venn diagram illustrating a total of 3747 differentially expressed probesets in three pairwise comparisons composed by HCV-ACR (acute cellular rejection in HCV infected patients), HCV recurrence, and chronic HCV liver biopsy samples. B. Heatmap and dendrogram resulting from agglomerative hierarchical clustering using Ward's method, using 1-Pearson's correlation for distance measure.

Mentions: As a first approach, differentially expressed genes were evaluated in ACR and HCV recurrence liver biopsy samples from HCV-infected recipients using oligonucleotide GeneChip® (Affymetrix Inc., CA, USA). The study was approved by the Institutional Review Board at Virginia Commonwealth University, and informed consents were obtained from all patients. The patients cohort included liver biopsy samples from 24 HCV-recipients with histological diagnosis of HCV recurrence disease (n = 13) and ACR in the setting of HCV (HCV-ACR; n = 11). Liver tissue from chronic HCV-infected patients without LT (Chronic-HCV; n = 10) were included for comparison analysis proposes. Tissue collection, total RNA isolation and quality control criteria, cDNA synthesis, in vitro transcription for labeled cRNA probe, and microarray hybridization and analysis were performed as described previously [22]. No significant differences in patient age and histological inflammatory activity index were identified between groups. All patients were Caucasian, male and infected with HCV genotype 1b. From the analysis, 3747 probesets were found to be significantly differentially expressed among three pairwise comparisons (HCV-ACR vs. HCV recurrence; HCV-ACR vs. Chronic-HCV; Chronic-HCV vs. HCV recurrence). Of those, 164 probesets were found to be differentially expressed between HCV-ACR and HCV-recurrence alone samples. Thirteen probe sets were found unique for both conditions (Figure 2A). Gene ontology and gene interaction analyses were performed using Ingenuity Pathways Analysis tools http://www.ingenuity.com. Those differentially expressed genes in ACR biopsy samples were associated with pathways involved in immune and inflammatory responses, apoptosis, complement system, and growth factor receptors. HCV recurrence samples revealed predominantly gene expression patterns associated with cell cycle and cell division, cell proliferation and blood coagulation. The supervised hierarchical clustering analysis including specific probesets differentially expressed for HCV-ACR vs. HCV recurrence clustered all samples in two well-differentiated groups characterizing both different post-LT conditions (Figure 2B). This first analysis clearly demonstrates the potential efficacy of gene expression analysis to differentiate ACR from HCV recurrence post-LT [13].


Biomarkers of disease differentiation: HCV recurrence versus acute cellular rejection.

Gehrau R, Mas V, Archer K, Maluf D - Fibrogenesis Tissue Repair (2012)

Molecular characterization of HCV-infected liver biopsy samples diagnosed with ACR or HCV recurrence. A. Venn diagram illustrating a total of 3747 differentially expressed probesets in three pairwise comparisons composed by HCV-ACR (acute cellular rejection in HCV infected patients), HCV recurrence, and chronic HCV liver biopsy samples. B. Heatmap and dendrogram resulting from agglomerative hierarchical clustering using Ward's method, using 1-Pearson's correlation for distance measure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368799&req=5

Figure 2: Molecular characterization of HCV-infected liver biopsy samples diagnosed with ACR or HCV recurrence. A. Venn diagram illustrating a total of 3747 differentially expressed probesets in three pairwise comparisons composed by HCV-ACR (acute cellular rejection in HCV infected patients), HCV recurrence, and chronic HCV liver biopsy samples. B. Heatmap and dendrogram resulting from agglomerative hierarchical clustering using Ward's method, using 1-Pearson's correlation for distance measure.
Mentions: As a first approach, differentially expressed genes were evaluated in ACR and HCV recurrence liver biopsy samples from HCV-infected recipients using oligonucleotide GeneChip® (Affymetrix Inc., CA, USA). The study was approved by the Institutional Review Board at Virginia Commonwealth University, and informed consents were obtained from all patients. The patients cohort included liver biopsy samples from 24 HCV-recipients with histological diagnosis of HCV recurrence disease (n = 13) and ACR in the setting of HCV (HCV-ACR; n = 11). Liver tissue from chronic HCV-infected patients without LT (Chronic-HCV; n = 10) were included for comparison analysis proposes. Tissue collection, total RNA isolation and quality control criteria, cDNA synthesis, in vitro transcription for labeled cRNA probe, and microarray hybridization and analysis were performed as described previously [22]. No significant differences in patient age and histological inflammatory activity index were identified between groups. All patients were Caucasian, male and infected with HCV genotype 1b. From the analysis, 3747 probesets were found to be significantly differentially expressed among three pairwise comparisons (HCV-ACR vs. HCV recurrence; HCV-ACR vs. Chronic-HCV; Chronic-HCV vs. HCV recurrence). Of those, 164 probesets were found to be differentially expressed between HCV-ACR and HCV-recurrence alone samples. Thirteen probe sets were found unique for both conditions (Figure 2A). Gene ontology and gene interaction analyses were performed using Ingenuity Pathways Analysis tools http://www.ingenuity.com. Those differentially expressed genes in ACR biopsy samples were associated with pathways involved in immune and inflammatory responses, apoptosis, complement system, and growth factor receptors. HCV recurrence samples revealed predominantly gene expression patterns associated with cell cycle and cell division, cell proliferation and blood coagulation. The supervised hierarchical clustering analysis including specific probesets differentially expressed for HCV-ACR vs. HCV recurrence clustered all samples in two well-differentiated groups characterizing both different post-LT conditions (Figure 2B). This first analysis clearly demonstrates the potential efficacy of gene expression analysis to differentiate ACR from HCV recurrence post-LT [13].

Bottom Line: Liver Transplantation (LT) is the optimal surgical treatment for HCV-cirrhotic patients at end-stage liver disease.The accurate differential diagnosis between both conditions is critical for treatment choice, and similar histological features represent a challenge for pathologists.Whole-genome gene expression (WGE) analyses through well-defined oligonucleotide microarray platforms represent a powerful tool for the molecular characterization of biological process.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of Virginia, Department of Surgery, Transplant Division, P.O. Box 800625, 904 Lane Rd, Charlottesville, VA, 22908-0625, USA.

ABSTRACT
The wound-healing process induced by chronic hepatitis C virus (HCV) infection triggers liver damage characterized by fibrosis development and finally cirrhosis. Liver Transplantation (LT) is the optimal surgical treatment for HCV-cirrhotic patients at end-stage liver disease. However, acute cellular rejection (ACR) and HCV recurrence disease represent two devastating complications post-LT. The accurate differential diagnosis between both conditions is critical for treatment choice, and similar histological features represent a challenge for pathologists. Moreover, the HCV recurrence disease severity is highly variable post-LT. HCV recurrence disease progression is characterized by an accelerated fibrogenesis process, and almost 30% of those patients develop cirrhosis at 5-years of follow-up. Whole-genome gene expression (WGE) analyses through well-defined oligonucleotide microarray platforms represent a powerful tool for the molecular characterization of biological process. In the present manuscript, the utility of microarray technology is applied for the ACR and HCV-recurrence biological characterization in post-LT liver biopsy samples. Moreover, WGE analysis was performed to identify predictive biomarkers of HCV recurrence severity in formalin-fixed paraffin-embedded liver biopsies prospectively collected.

No MeSH data available.


Related in: MedlinePlus