Expression And Clinical Significance Of Ascites MiR-21/143/145/155/200a In Liver Cirrhosis

Background and Aims: A few research groups have uncovered the value of circulating microRNA(miRNA)as a biochemical molecular marker for cancer.However,to our knowledge,there are no reasearches on the importance of ascites microRNA in liver cirrhosis.The purpose of this reasearch was to investigate the significance of ascites miR-21,miR-143,miR-145,miR-155,miR-200 a expression level as a molecular marker for hepatitis B cirrhosis to identify the benign and malignant ascites.Method:16 patients with hepatocellular carcinoma(HCC)and 66 patients with liver cirrhosis were enrolled in this study.All of patients were Hepatitis B Virus(HBV)infected and the date of clinical materials were collected.Ascites was collected and total RNA was isolated from ascites.Five miRNAs(miR-21,miR-143,miR-145,miR-155,miR-200a)levels were measured in ascites by quantitative polymerase chain reaction.The expression levels of these miRNAs were analyzed in hepatitis B cirrhosis and HCC patients.The power of those miRNAs in differentiating hepatocellular carcinoma from cirrhosis by receiver operating charactrisistic(ROC)and area under curve(AUC).Ordinal logistic regression analysis was conducted to assess the association of miRNAs expression with hepatocellular carcinoma.Result : Compared with hepatitis B cirrhosis,ascites miR-21 level in the patients with HCC was noted significantly higher(P=0.003),on the contrary,the levels of miR-143,miR-145,miR-200 a were noted lower(P=0.026,P=0.003,P=0.045,respectively),but the expression of miR-155 showed no difference in hepatocellular carcinoma patients(P>0.05).In hepatitisB cirrhosis patients,we found three miRNAs(miR-21,miR-155,miR-200a)reduced expression levels in anti-virus therapy patients compared with untreated(P=0.014,P=0.001,P=0.027,respectively).The expression of miR-155 was negatively correlated with child-pugh classification(r=-2.65,P=0.022).However,the other four miRNAs(miR-21,miR-145,miR-155,miR200a)showed no correlation with ascites ADA/ LDH/albumin,AFP,HBV-DNA,or Child-Pugh classification(P>0.05).The ascites expression of miR-143,miR-145,miR-155 and miR200 a were significantly correlated.And logistic regression analysis revealed the miR-21 overexpression was independent risk factor for the HCC(P=0.010).The subsequent analysis revealed five diagnostic miRNA signatures enabling to distinguish HCC.When differentiating HCC from hepatitis B cirrhosis,ROC analysis of ascites miR-21 yielded an AUC,sensitivity and specificity respectively was 0.7 7 4,6 8.8 %,8 0.3 %.Th e mi R-1 4 3 wi t h mi R-1 4 5,mi R-1 4 5 wi t h miR-155,miR-145 with miR-200 a,miR-155 with miR200 a diagnostic values of the AUC in HCC respectively were 0.730,0.715,0.716,0.685.And miR-145+miR200a haved the highest diagnostic sensitivity was 81.3%.Conclusions: First,miR-21,miR-143,miR-145,miR-145,miR-200 a may participate in the process of hepatocelluar carcinoma,they have considerable value in diagnosing malignant ascites of hepatocellular carcinoma and they can be used as potential biochemical marker in the identfication of benign and malignant ascites of hepatitis B cirrhosis.Second,miR-21 has the highest specificity for diagnosing the malignant ascites of hepatocellular carcinoma,miR-21 overexpression is the risk factor for hepatocellular carcinoma.It is suggested that miR-21 has clinical value as a biochemical marker in the identification of benign and malignant ascites of hepatitis B cirrhosis.