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Abstract

Purpose: Up to 25% of chronic hepatitis B (CHB) patients even-tually develop hepatocellular carcinoma (HCC), a disease with poor prognosis unless detected early. This study identifies a blood based RNA biomarker panel for early HCC detection in CHB.Materials and Methods: A genome-wide RNA expression study was performed using RNA extracted from blood samples from Malaysian patients (matched HCC, CHB, controls). Genes differ-entiating HCC from controls were selected for further testing using quantitative real-time polymerase chain reaction. Finally, a 6-gene
biomarker panel was identified and characterized using a training set (cohort I = 126), and tested against 2 test sets (cohort II = 222; cohort III = 174). The total number of samples used for each group is: HCC + CHB = 143, CHB = 211, control = 168.

Results: Our gene panel displays a consistent trend distinguishing HCC from controls in our test sets, with an area under receiver- operating characteristic curve of 0.9 in cohort III. Our independent test set (cohort III) showed that the gene panel had a sensitivity of 70% with a specificity of 92%. The biomarker profile for HCC was consistently detected in a small subgroup of CHB patients, thus potentially predicting early, preclinical cases of cancer that should be screened more intensively.
Conclusion: The biomarkers identified in this study can be used as the basis of a blood-based test for the detection of early HCC in CHB.




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