Molecular profiles of HCV cirrhotic tissues derived in a panel of markers with clinical utility for hepatocellular carcinoma surveillance

Ricardo C. Gehrau, Kellie J. Archer, Valeria Mas, Daniel Maluf

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Early hepatocellular carcinoma (HCC) detection is difficult because low accuracy of surveillance tests. Genome-wide analyses were performed using HCV-cirrhosis with HCC to identify predictive signatures. Methodology/Principal Findings: Cirrhotic liver tissue was collected from 107 HCV-infected patients with diagnosis of HCC at pre-transplantation and confirmed in explanted livers. Study groups included: 1) microarray hybridization set (n = 80) including patients without (woHCC = 45) and with (wHCC = 24) HCC, and with incidental HCC (iHCC = 11); 2) independent validation set (n = 27; woHCC = 16, wHCC = 11). Pairwise comparisons were performed using moderated t-test. FDR<1% was considered significant. L1-penalized logistic regression model was fit for woHCC and wHCC microarrays, and tested against iHCC. Prediction model genes were validated in independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progressing to mitosis; unregulated DNA damage check-points, and apoptosis. The prediction model included 17 molecules demonstrated 98.6% of accuracy and correctly classified 6 out of 11 undiagnosed iHCC cases. The best model performed even better in the additional independent set. Conclusions/Significances: The molecular analysis of HCV-cirrhotic tissue conducted to a prediction model with good performance and high potential for HCC surveillance.

Original languageEnglish (US)
Article numbere40275
JournalPloS one
Volume7
Issue number7
DOIs
StatePublished - Jul 5 2012

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hepatoma
Hepatocellular Carcinoma
Biomarkers
Tissue
monitoring
Microarrays
Liver
Genes
prediction
Cells
cell cycle
Logistic Models
Cell death
microarray technology
liver
Inborn Genetic Diseases
Gene expression
genetic disorders
Logistics
Cell Cycle Checkpoints

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Molecular profiles of HCV cirrhotic tissues derived in a panel of markers with clinical utility for hepatocellular carcinoma surveillance. / Gehrau, Ricardo C.; Archer, Kellie J.; Mas, Valeria; Maluf, Daniel.

In: PloS one, Vol. 7, No. 7, e40275, 05.07.2012.

Research output: Contribution to journalArticle

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abstract = "Background: Early hepatocellular carcinoma (HCC) detection is difficult because low accuracy of surveillance tests. Genome-wide analyses were performed using HCV-cirrhosis with HCC to identify predictive signatures. Methodology/Principal Findings: Cirrhotic liver tissue was collected from 107 HCV-infected patients with diagnosis of HCC at pre-transplantation and confirmed in explanted livers. Study groups included: 1) microarray hybridization set (n = 80) including patients without (woHCC = 45) and with (wHCC = 24) HCC, and with incidental HCC (iHCC = 11); 2) independent validation set (n = 27; woHCC = 16, wHCC = 11). Pairwise comparisons were performed using moderated t-test. FDR<1{\%} was considered significant. L1-penalized logistic regression model was fit for woHCC and wHCC microarrays, and tested against iHCC. Prediction model genes were validated in independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progressing to mitosis; unregulated DNA damage check-points, and apoptosis. The prediction model included 17 molecules demonstrated 98.6{\%} of accuracy and correctly classified 6 out of 11 undiagnosed iHCC cases. The best model performed even better in the additional independent set. Conclusions/Significances: The molecular analysis of HCV-cirrhotic tissue conducted to a prediction model with good performance and high potential for HCC surveillance.",
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