ABSTRACT
Background: Circulating microRNAs [miRNAs] are endogenous, small [17-25 nucleo-tides] non-coding RNAs that are overexpressed in many human cancers including hepatocellular carcinoma [HCC]. Moreover, circulating miRNAs can reflect the level of tissue miRNAs, so could be potential tumor markers. miRNA-21 regulates post-transcriptional expression of tumor suppressor gene; programed cell death 4 [PDCD4] gene which implies that miRNA-21 might be a novel diagnostic and/or prognostic marker for cancer
Objective: To evaluate the diagnostic and prognostic potential of circulating miRNA-21 and study the expression of PDCD4 gene as a target of miRNA-21 in HCC in Egyptian patients
Subjects and methods: This study was conducted on 30 HCC patients, 20 chronic liver disease [CLD] patients due to HCV infection and 20 healthy subjects. Serum alpha fetoprotein [AFP] was measured for all participants. The relative plasma expression of each of miRNA-21 and PDCD4 gene was determined in whole blood samples using real-time polymerase chain reaction
Results: The results revealed over expression of miRNA-21 and under expression of PDCD4 gene in HCC group [p < 0.05] compared to both CLD and healthy subjects, while no significant change was detected between CLD and healthy subjects. miRNA-21 expression was negatively correlated with PDCD4 gene expression. miRNA-21 expression increased significantly with presence of cirrhosis, increased number of focal lesions, larger size of tumor, advanced tumor stage and presence of vascular invasion. Receiver Operator of Characteristics [ROC] curve analysis of plasma miRNA-21 revealed that, at a cut-off value of 3.93 [fold expression], the sensitivity and specificity for differentiation of HCC cases were 93% and 90%, respectively
Conclusion: Circulating miRNA-21 could be a novel early diagnostic and prognostic biomarker for detection of HCC. Approaches interfering with the miRNA-2 l/PDCD4-axis, or releasing PDCD4 expression, may have a strong basis for therapeutic uses in cancer in the future