Plasma Circular RNA Panel to Diagnose Hepatitis B Virus-Related Hepatocellular Carcinoma

To explore whether plasma circular RNAs (circRNAs) can diagnose hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), microarray and qPCR were used to identify plasma circRNAs that were increased in HCC patients compared with controls (including healthy controls, chronic hepatitis B, HBV-related liver cirrhosis and HCC patients). A logistic regression model was constructed using a training set (n=313) and then validated using another two independent sets (n=306 and 526, respectively). Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. We identified a plasma circRNA panel (CircPanel) containing three circRNAs (hsa_circ_0000976, hsa_circ_0007750 and hsa_circ_0139897) that could detect HCC. CircPanel showed a higher accuracy than AFP (alpha-fetoprotein) to distinguish individuals with HCC from controls in all three sets (AUC 0.863 [95% CI 0.819–0.907] vs 0.790 [0.738–0.842], P=0.036 in training set; 0.843 [0.796–0.890] vs 0.747 [0.691–0.804], P=0.011 in validation set 1 and 0.864 [0.830–0.898] vs 0.769 [0.728–0.810], P<0.001 in validation set 2). CircPanel also performed well in detecting Small-HCC (solitary, ≤3cm), AFP-negative HCC and AFP-negative Small-HCC. Significance of this study What is already known about this subject? The diagnostic accuracy of alpha-fetoprotein (AFP) in detecting hepatocellular carcinoma (HCC) is unsatisfactory. Circular RNA (circRNA) expression profiles in HCC and adjacent nontumor liver tissues are significantly different. Plasma circRNAs are enriched, stable and can be biomarkers for various diseases. What are the new findings? The expression of circRNAs in the plasma from HCC patients and chronic hepatitis B is significantly different. Plasma circRNA panel (CircPanel, including hsa_circ_0000976, hsa_circ_0007750 and hsa_circ_0139897) has a higher accuracy than AFP to distinguish individuals with HCC or Small-HCC (solitary, ≤3cm) from controls (healthy controls, chronic hepatitis B and HBV-related liver cirrhosis). CircPanel also performs well in diagnosing AFP-negative HCC and AFP-negative Small-HCC. How might it impact on clinical practice in the foreseeable future? Plasma CircPanel can be a diagnostic biomarker in detecting HCC and improves the diagnostic accuracy.