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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

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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, miRNA-199a, 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 miRNA-122, 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 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 miR-16 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.

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Acknowledgments

This study was funded by Cairo University and there is no conflict of interest among the authors of this research; Nevine E. EL-Abd, Nahla A. Fawzy, Suzan M. EL-Sheikh and Mohamed E. Soliman. This research was funded by Cairo University as the only party and there is no conflict of interest among the authors of this study.

Authors contributions

Nevine E. EL-Abd (corresponding author): contributed in laboratory methodology, statistical analysis of data and writing the paper. Nahla A. Fawzy: contributed in analysis of results and writing the paper. Suzan M. EL-Sheikh: contributed in laboratory methodology, analysis of data and writing the paper. Mohamed E. Soliman: contributed in subjects selection (patients and controls) and all the clinical and radiological assessment of patients and clinical staging of HCC. The guarantor for the overall content is: Suzan M. EL-Sheikh

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Authors and Affiliations

  1. Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt

    Nevine E. EL-Abd, Nahla A. Fawzy, Suzan M. EL-Sheikh & Mohamed E. Soliman

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  1. Nevine E. EL-Abd
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  2. Nahla A. Fawzy
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  3. Suzan M. EL-Sheikh
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Correspondence to Nevine E. EL-Abd.

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EL-Abd, N.E., Fawzy, N.A., EL-Sheikh, S.M. et al. 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. Mol Diagn Ther 19, 213–220 (2015). https://doi.org/10.1007/s40291-015-0148-1

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  • DOI: https://doi.org/10.1007/s40291-015-0148-1

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