Clinical Utility of Telomerase mRNA in the Diagnosis of Hepatocellular Carcinoma by Real-Time Polymerase Chain Reaction

Abstract

Hepatocellular carcinoma (HCC) is the sixth most common neoplasm worldwide and the third most frequent cause of cancer-related death. The major risk factor associated with HCC is liver cirrhosis, which is predominantly caused by chronic HBV and/or HCV infections, aflatoxin B1 exposure, and alcoholic liver disease. It is estimated that HBV and HCV account for approximately 75%-80% of HCC cases worldwide. The diagnosis of HCC is mainly based on a combination of abdominal ultrasound and serum alpha-fetoprotein level. However, tumors that are too small will be missed by abdominal ultrasound, and serum alpha fetoprotein level has a low sensitivity particularly in early-stage disease. Clearly, the available screening methods are inadequate for early detection and follow up of HCC. So there is a need for a higher sensitivity aiming at early diagnosis of HCC as well as a better specificity aiming at differentiation between HCC and benign lesions. Telomerase is a specialized ribonucleoprotein polymerase, composed of RNA subunit (human telomerase RNA, hTR) and a catalytic protein (human telomerase reverse transcriptase, hTERT) which can elongate telomeric DNA using its own RNA subunit as a template. TERT activity is generally found in stem cells, hematopoietic progenitor cells, activated lymphocytes and fetal cells. TERT activity was found to be absent in most normal human somatic cells but present in cancerous cells where progressive telomere shortening is halted and thus, the cells become immortal. In this regard, our study aimed to evaluate the clinical utility of TERT mRNA in the diagnosis and prognosis of HCC and to correlate its levels with AFP, the routinely used serological marker, for diagnosis of the disease nowadays. This study was conducted at the Tropical Medicine and Clinical Pathology Departments of Ain Shams University Hospitals on 50 hepatic patients in addition to 20 apparently healthy age-matched controls. Patients were divided into two groups according to their diagnosis. Group Ia included 30 HCC patients who were further subdivided into three subgroups based on the stage of the disease, as determined by the BCLC Staging System (10 patients in stage A, 10 patients in stage B, 10 patients in stage D). Group Ib included 20 patients with liver cirrhosis. All patients in the study were subjected to full history taking, thorough clinical examination, radiological investigations including abdominal U/S and CT scan, routine laboratory investigations (ALT, AST, serum albumin, total bilirubin, conjugated bilirubin and INR) in addition to serum AFP and TERT mRNA assay by real-time polymerase chain reaction technique.