Molecular Diagnosis of Hepatocellular Carcinoma in Egypt

Document Type : Original Article

Authors

1 Department of Clinical Biochemistry,National Liver Institute

2 Department of Clinical Pathology, National Liver Institute

3 Department of Hepatology, National Liver Institute

4 Department of Molecular Diagnostics, Genetic Engineering and Biotechnology Research Institute - University of Sadat City, Egypt

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. It is a prevalent cancer that often develops in patients with chronic hepatitis and cirrhosis in association with hepatitis B or C virus infection. Diagnostic modalities such as tumor markers, ultrasonography and CT have contributed to its earlier diagnosis but remain not sensitive enough. Telomeres are specializes structures at the ends of eukaryotic chromosomes and lead to their stabilization. Telomerase is a ribonucleoprotein enzyme responsible for replication of telomeres at chromosomal ends in most eukaryotes.Its RNA subunit provides the template for addition of (GGTTAG) repeats to chromosome ends .Human telomerase mRNA (hTERT- mRNA)has been identified in many cancers and claimed to be reactivated in HCC.
Aim: to investigate Human telomerase mRNA (hTERT- mRNA) in peripheral blood of hepatocellular carcinoma (HCC) and chronic liver diseases (CLD) patients,To correlate the level of Human telomerase mRNA (hTERT- mRNA) with alpha feto –protein ( AFP),the traditional serological marker for HCC.
Patients and methods:The study was conducted on 60 patients selected from the National Liver Institute clinics and inpatients hepatology department. The patients were divided into group I (30 patients with CLD) and group II (30 patients diagnosed to have HCC). In addition to group III that comprised 20 apparantly healthy volunteers .All selected individuals were subjected to history taking ,thorough clinical examination, abdominal ultrasonography and routine laboratory investigations as liver function tests ,CBC, hepatitis viral markers , serum AFP and quantitative detection of m-RNA expression encoding for telomerase catalytic subunit hTERT by real time PCR measurement using 7500 Real Time PCR System(Applied Biosystems).
Results: A significant elevation in AFP level in HCC group when compared to CLD patients group or to control group (p < 0.01).The mean level of hTERT m-RNA expression in HCC patients group was significantly higher than both CLD patients group and controls (p<0.01). An hTERT m-RNA expression cut off level of 81.5 copies /ml showed prediction of HCC 100% sensitivity,95 % specificity, accuracy 99.6% ,standard error (SE) was 0.003 and confidence interval (CI) was (0.99- Conclusion: Real time assay of hTERT m-RNA in patients with CLD could be used as a satisfactory molecular marker for diagnosis of HCC. hTERT m-RNA is thought to be superior to AFP for early detection of HCC.

Keywords

References

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