Circulating MiRNA-21 and programed cell death (PDCD) 4 gene expression in hepatocellular carcinoma (HCC) in Egyptian patients
Background: Circulating microRNAs (miRNAs) are endogenous, small (17–25 nucleotides) 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-21/PDCD4-axis, or releasing PDCD4 expression, may have a strong basis for therapeutic uses in cancer in the future.