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

Zhou, W.-p.; Yu, J.; Wang, M.-c.; Ding, W.-b.; Guo, X.-g.; Xu, J.; Xu, Q.-g.; Yang, Y.; Sun, S.-h.; Liu, J.; Qin, L.-x.; Liu, H.; Yang, F.

doi:10.1101/576751

bioRxiv · 10.1101/576751

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

Zhou, W.-p.·Yu, J.·Wang, M.-c.·Ding, W.-b.·Guo, X.-g.·Xu, J.·Xu, Q.-g.·Yang, Y.·Sun, S.-h.·Liu, J.·Qin, L.-x.·Liu, H.·Yang, F.

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Abstract

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.\n\nSignificance of this studyWhat is already known about this subject? O_LIThe diagnostic accuracy of alpha-fetoprotein (AFP) in detecting hepatocellular carcinoma (HCC) is unsatisfactory.\nC_LIO_LICircular RNA (circRNA) expression profiles in HCC and adjacent nontumor liver tissues are significantly different.\nC_LIO_LIPlasma circRNAs are enriched, stable and can be biomarkers for various diseases.\nC_LI\n\nWhat are the new findings? O_LIThe expression of circRNAs in the plasma from HCC patients and chronic hepatitis B is significantly different.\nC_LIO_LIPlasma 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).\nC_LIO_LICircPanel also performs well in diagnosing AFP-negative HCC and AFP-negative Small-HCC.\nC_LI\n\nHow 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.

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Zhou, W.-p., Yu, J., Wang, M.-c., Ding, W.-b., Guo, X.-g., Xu, J., Xu, Q.-g., Yang, Y., Sun, S.-h., Liu, J., Qin, L.-x., Liu, H., Yang, F.. 2019-03-14. Plasma Circular RNA Panel to Diagnose Hepatitis B Virus-Related Hepatocellular Carcinoma. https://doi.org/10.1101/576751

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