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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

Supervised hierarchical clustering for HCV-ACR, ACR-alone, and HCV recurrence diagnosed liver biopsy samples. The dendrogram illustrates clustered samples using Ward's method when a total of 80 differentially expressed probesets are included. ACR samples from no-HCV-infected recipients are highlighted in grey boxes.
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Figure 3: Supervised hierarchical clustering for HCV-ACR, ACR-alone, and HCV recurrence diagnosed liver biopsy samples. The dendrogram illustrates clustered samples using Ward's method when a total of 80 differentially expressed probesets are included. ACR samples from no-HCV-infected recipients are highlighted in grey boxes.

Mentions: In a second approach, a similar analysis was performed by increasing the number of samples. A total of 51 biopsy samples from unique HCV-infected recipients were included in the analysis. A training set composed by 32 ACR liver samples from HCV-infected recipients and 2 ACR liver samples from no HCV-infected recipients (n =34), were evaluated using microarray techniques. From the analysis, 179 probesets were found significantly differentially expressed among HCV-ACR, no-HCV-ACR, and HCV recurrence biopsy samples. A total of 71 exclusive genes were identified for HCV-ACR vs. HCV recurrence pairwise comparison. Interestingly, no significant probesets were found differentially expressed between ACR samples from HCV and no-HCV infected recipients, which suggest a particular ACR molecular nature independent of the HCV infection. Gene ontology analysis identified canonical pathways specifically associated to a cytotoxic T cell profile in for HCV recurrence samples, and inflammatory response related genes as the ACR profile. The supervised clustering analysis including probesets (n = 80) representing those 71 specific genes displayed two well-differentiated groups for ACR and HCV recurrence samples. Interestingly, no-HCV-ACR samples were clustered within the HCV-ACR group (Figure 3).


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

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

Supervised hierarchical clustering for HCV-ACR, ACR-alone, and HCV recurrence diagnosed liver biopsy samples. The dendrogram illustrates clustered samples using Ward's method when a total of 80 differentially expressed probesets are included. ACR samples from no-HCV-infected recipients are highlighted in grey boxes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Supervised hierarchical clustering for HCV-ACR, ACR-alone, and HCV recurrence diagnosed liver biopsy samples. The dendrogram illustrates clustered samples using Ward's method when a total of 80 differentially expressed probesets are included. ACR samples from no-HCV-infected recipients are highlighted in grey boxes.
Mentions: In a second approach, a similar analysis was performed by increasing the number of samples. A total of 51 biopsy samples from unique HCV-infected recipients were included in the analysis. A training set composed by 32 ACR liver samples from HCV-infected recipients and 2 ACR liver samples from no HCV-infected recipients (n =34), were evaluated using microarray techniques. From the analysis, 179 probesets were found significantly differentially expressed among HCV-ACR, no-HCV-ACR, and HCV recurrence biopsy samples. A total of 71 exclusive genes were identified for HCV-ACR vs. HCV recurrence pairwise comparison. Interestingly, no significant probesets were found differentially expressed between ACR samples from HCV and no-HCV infected recipients, which suggest a particular ACR molecular nature independent of the HCV infection. Gene ontology analysis identified canonical pathways specifically associated to a cytotoxic T cell profile in for HCV recurrence samples, and inflammatory response related genes as the ACR profile. The supervised clustering analysis including probesets (n = 80) representing those 71 specific genes displayed two well-differentiated groups for ACR and HCV recurrence samples. Interestingly, no-HCV-ACR samples were clustered within the HCV-ACR group (Figure 3).

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