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


RESULTS
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. L(1)-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
The molecular analysis of HCV-cirrhotic tissue conducted to a prediction model with good performance and high potential for HCC surveillance.
University of Virginia, Department of Surgery, Transplant Division. Charlottesville, Virginia, United States of America.
Ricardo C
RC
Gehrau
Kellie J
KJ
Archer
Valeria R
VR
Mas
Daniel G
DG
Maluf
D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000378:metabolism* / Q000821:virology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D055088:Early Detection of Cancer; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000821:virology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000821:virology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000821:virology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis / Q000592:standards; D059467:Transcriptome
D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins