Plasma circular RNA panel to diagnose hepatitis B virus‐related hepatocellular carcinoma: A large‐scale, multicenter study.

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 HBV‐related HCC patients compared to controls (including healthy controls, chronic hepatitis B and HBV‐related liver cirrhosis). 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% confidence interval, 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, ≤3 cm), AFP‐negative HCC and AFP‐negative Small‐HCC. What's new? To date, one limitation in the treatment of hepatocellular carcinoma (HCC) is the lack of serum biomarkers with satisfactory diagnostic accuracy. Here, the authors explored whether plasma circRNAs can be biomarkers to diagnose hepatitis B virus‐related HCC in 1155 participants from three hospitals in China. They identified a plasma circRNA panel (CircPanel, including hsa_circ_0000976, hsa_circ_0007750, and hsa_circ_0139897) that showed higher accuracy than the clinically‐used serum biomarker AFP in distinguishing individuals with HCC or Small‐HCC from controls and performed well in diagnosing AFP‐negative HCC and AFP‐negative Small‐HCC. Altogether, the findings point to CircPanel as a promising potential biomarker in HCC diagnosis. [ABSTRACT FROM AUTHOR]