Circular RNA 0006602 in plasma exosomes: a new potential diagnostic biomarker for hepatocellular carcinoma

Circular RNAs (circRNAs) in exosomes exhibit stable expression and are not easily degraded in plasma; a characteristic that makes them ideal as novel non-invasive tumor diagnostic markers. In this study, we examined different expression of circRNA in plasma exosomes of primary hepatocellular carcinoma patient and healthy volunteer by full transcriptome sequencing. Five circRNAs with up-regulated expression were selected, and large sample size verified their expression. Among them, it is further confirmed that exo_circ_0006602 is up-regulated in the large sample cohort. In addition, the expression level of exo_circ_0006602 was correlated with HBsAg (P<0.011), HBeAg (P=0.048), liver cirrhosis (P=0.001) and Edmondson-Steiner grade (P<0.001). The receiver operating characteristic (ROC) was used to evaluate the accuracy of exo_circ_0006602 as a diagnostic marker. The AUC value of exo_circ_0006602 was significantly highter than common serum tumor markers AFP and CEA. Exo_circ_0006602 combined with AFP can significantly improve the diagnostic accuracy. Cell function experiments show that exo_circ_0006602 can significantly improve the proliferation and invasion ability of liver cancer cell lines and also promoted the expression of tumor proliferation-related protein Snail. In conclusion, our results suggested that exo_circ_0006602 can be used as a potential non-invasive biomarker for the early diagnosis and screening of liver cancer, the sensitivity and specificity of diagnosis are higher than traditional tumor markers.