Molecular Detection of Human Telomerase mRNA (hTERT-mRNA) in Egyptian Patients with Hepatocellular Carcinoma

Background and Aims: Diagnostic modalities for hepatocellular carcinoma (HCC) as markers, sonography, and CT have contributed to the early detection of HCC but are still not sensitive enough. Human telomerase RNA subunit (hTERT-mRNA) has been identified in many cancers and claimed to be reactivated in HCC. To investigate hTERT-mRNA in the peripheral blood of HCC and chronic liver disease (CLD) patients and correlate its level with alpha feto protein (AFP), the serological marker for HCC.

Methods: The study was conducted on 44 patients selected from the National Liver Institute. Patients included Group I (22 patients diagnosed to have HCC), Group II (22 patients with CLD), and 12 apparently healthy volunteers as controls (Group III). All selected individuals were subjected to history taking, a clinical examination, abdominal sonography and laboratory investigations as liver function tests (LFTs), cell blood count (CBC), hepatitis viral markers, AFP, and real-time polymerase chain reaction (PCR) Quantitative detection of -mRNA expression, encoding for telomerase catalytic subunit.

Results: There was a significant elevation of AFP levels in the HCC group compared to both the CLD and control groups (P < 0.00, P < 0.001). The mean hTERT-mRNA expression in HCC patients was significantly higher than both CLD patients and controls (P < 0.001, P < 0.001). hTERT-mRNA was correlated with AFP and tumor size (P < 0.05, P < 0.001). The AFP cutoff level (185 ng/ml) resulted in a 63.6% sensitivity, a 85.3% specificity; a 89.3% positive predictive value (PPV) level, a 76.2 % negative predictive value (NPV) level and a 83.4% accuracy for HCC prediction. The hTERT-mRNA cutoff level (112.5 copies/ml) showed a 77.3% sensitivity, a 97.1% specificity, a 98% PPV level, a 79.2 % NPV level, and an accuracy of 84% for HCC prediction. Combining hTERT-mRNA and AFP increased diagnostic accuracy to 90.5%. Both markers had a 84.1% sensitivity, a 86.4% specificity, a 86.4% PPV level, and a 88.3 % NPV level.

Conclusions: hTERT-mRNA is thought to be superior to AFP in CLD patients and could be a marker for the early diagnosis of HCC. Combined hTERT-mRNA and AFP would augment early detection and successful follow-up of HCC patients.