Urinary circular RNA panels to help diagnose hepatitisB virus–related hepatocellular carcinoma: a multi-center, large scale and case-control study

Abstract

Abstract Background: Over 60% of patients with hepatocellular carcinoma (HCC) do not receive curative therapitics due to late clinical manifestations and diagnosis. The 5-year survival rate for advanced HCC is around 2%. Curative therapies for early HCC can improve the 5-year survival rate to over 70%.We aimed to develop sensitive and noninvasive biomarkers in urine for detecting HCC. Methods: Totally, 1254 participants were recruited and randomly allocated into three independent cohorts [healthy controls, chronic hepatitis B (CHB), HBV-induced liver cirrhosis and HBV-related HCC].14 circular RNAs(circRNAs) were chosen as putative biomarkers in urine due to their differential expressions in HCC tissue and blood after analyzing related published reports. Their expression levels in urine were measure by quantitative polymerase chain reaction (qPCR). Logistic regression models were made using a training cohort (n = 312) and then validated using an independent cohort (n = 741). Area under the receiver operating characteristic (ROC) curve (AUC) was used to assess the diagnostic performances. Results: CircRNA panels (circ_0075792, circ_0005397 and circ_0000976) were obtained with high diagnostic performances of differentiating HCC from the three above control groups with sensitivities over 85% , specificity over 95% and AUC over 0.9. Conclusions: Urinary circRNA panels identified and validated from these results show desirable diagnostic performances for detecting HCC. Accordingly, HCC patients who would have otherwise missed the curative theraputic windows can benefit from the best theraputics.