| Objective: Through detection of expression of RNA(miRNA 200 a,miRNA 122,miRNA125,miRNA 10 b,miRNA 21,miRNA 92 b,lncRNA HOTAIR,lncRNA DANCR,lncRNA HOTTIP and lncRNA TCF7)in rats and patients with hepatocellular carcinoma.,to explore the clinical value of non-coding RNAs(ncRNAs)in Hepatocellular Carcinoma(HCC).Methods: HCC was induced with diethylnitrosamine in rats.Using a scoring system based on histological examination,six different stages(normal liver,degeneration,fibrosis,cirrhosis,early HCC and late HCC)were identified in the development of HCC.The expression levels of AFP and miRNAs(miRNA 10 b,miRNA 21,miRNA 122 and miRNA200a)were detected in both tissue and blood samples from those six stages.Receiver operating characteristic(ROC)curve analysis was conducted to evaluate the power of each parameter and their different combinations in diagnosing HCC.28 cases of HCC diagnosed by pathological section were collected.During the same period,12 patients with hepatic hemangioma as control group in our hospital were also recruited.Quantitative real-time PCR was used to evaluate the expression levels of microRNAs(miRNA 200 a,miRNA 122,miRNA 125,miRNA 10 b,miRNA 21 and miRNA 92b)and lncRNAs(lncRNA HOTAIR,lncRNA DANCR,lncRNA HOTTIP and lncRNA TCF7)in tumor tissues and serum of HCC patients.The diagnostic efficacy of ncRNAs in serum and tissue was evaluated by using the ROC.Results: The expressions of the selected four miRNAs at early stage of HCC development obtained more remarkably alterations than the level of AFP(P<0.05).During the liver fibrosis stage,the expression of miRNA 10 b was significantly elevated(P<0.05).In the cirrhosis stage,the expression of miRNA 21 was significantly elevated(P<0.05);serum levels of miRNA 200 a and miRNA 122 were significantly decreased(P<0.05).The different combinations of serous miRNAs had stronger power in predicting HCC than single AFP.There are higher levels of miRNA 10 b,miRNA 21,lncRNA DANCR and lncRNA TCF7 expressed in tissues of HCC as compared with their controls(P<0.05).There are lower levels of miRNA 122 in tissues of HCC as compared with their controls(P<0.05).The relative expression levels of miRNA 200 a,miRNA 125,miRNA 92 b in liver tissues of HCCpatients and control tissues were not significantly different.The expressions of miRNA 122 and miRNA 125 in HCC serum were significantly lower than those in hemangioma control group(P<0.05).The expression levels of miRNA 10 b,miRNA 21,miRNA 92 b,lncRNA DANCR and lncRNA HOTTIP in HCC serum were significantly higher than those in hemangioma control group(P<0.05).ROC analysis showed that combination of positively expressed miRNA 125,miRNA 10 b and lncRNA HOTTIP had a larger area under the curve(AUC)=0.994(95% CI: 0.978-1.000)compared to any of the ten selected markers and their different groups.Conclusion: To conclude,the combination of circulating ncRNAs might serve as promising biomarkers for HCC screening. |
