Circulating miRNA-122, miRNA-199a, and miRNA-16 as Biomarkers for Early Detection of Hepatocellular Carcinoma in Egyptia
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ORIGINAL RESEARCH ARTICLE
Circulating miRNA-122, miRNA-199a, and miRNA-16 as Biomarkers for Early Detection of Hepatocellular Carcinoma in Egyptian Patients with Chronic Hepatitis C Virus Infection Nevine E. EL-Abd1 • Nahla A. Fawzy1 • Suzan M. EL-Sheikh1 • Mohamed E. Soliman1
Ó Springer International Publishing Switzerland 2015
Abstract Background Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world. Having a very poor prognosis, it currently ranks as the third most common cause of cancer-related deaths. MiRNAs are a set of small, single-stranded, non-coding RNA molecules that negatively regulate gene expression at the post-transcriptional level. Several miRNAs were found to be frequently deregulated in HCC. Objective To investigate whether miRNA-122, miRNA199a, and miRNA-16 are altered in sera of hepatitis C virus (HCV)-induced HCC patients compared with chronic HCV patients without HCC, and to assess their diagnostic value to differentiate between HCC and chronic HCV in order to develop a non-invasive diagnostic and prognostic tool for HCC. Methods We analysed the expression of mature miRNA122, miRNA-199a, and miRNA-16 in serum by a singleplex TaqMan two-step stem loop quantitative real-time reverse-transcription PCR (qRT-PCR) in 40 newly diagnosed HCC patients and 40 chronic HCV liver cirrhosis patients, as well as 20 apparently healthy individuals as a control group, using RNU48 as a normalisation control. Results Serum miR-16 was significantly lower in HCC than in HCV patients (P = 0.033). The serum level of miR-199a in chronic HCV patients was significantly lower than in healthy controls (P = 0.001). Receiver operating curve (ROC) analysis for serum miRNA-16 for discriminating HCC from HCV patients showed that at the cut-off & Nevine E. EL-Abd [email protected]; [email protected] 1
Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt
value of 0.904, the sensitivity and specificity for this marker were 57.5 and 70 %, respectively. The combination of serum miR-16 with serum alpha fetoprotein (AFP) resulted in improved sensitivity to 85% and increased diagnostic accuracy to 87.5 %. Serum miR-199a and miR16 were significantly associated with several parameters of HCC such as tumour size and number. Conclusion The combination of serum miR-16 and serum AFP is a significant improvement on the current best practice of serum AFP for HCC in HCVpositive patients. Serum miR-199a and miR-16 could be used as potential indicators of the progress of HCC. Key Points MiRNA-122, miRNA-199a, and miRNA-16 as potential biomarkers of HCC in chronic HCV patients. MiRNA-16 and 199a are associated with the progress of disease in HCC patients. The combination of serum miR-16 and serum AFP could be used as a diagnostic tool for HCC.
1 Introduction Hepatocellular carcinoma (HCC) is reported to be the fifth most common cancer in men and the eighth most common cancer in women, with about 560,000 cases discovered every year, more than 80 % of which occur in developing countries. Having a very
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