الفهرس 
HEPATOCELLULARCARCINOMAOnly 14 pages are availabe for public view
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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.
Both AFP and TERT mRNA are significantly higher in HCC patients group compared to CLD patients and control groups.
The correlation analysis between AFP and other studied parameters in HCC patients revealed a highly significant positive correlation between AFP and TERT mRNA.
The correlation analysis between TERT mRNA and different studied parameters in HCC patients revealed a significant positive correlation between TERT mRNA, conjugated bilirubin, INR and AFP and a significant negative correlation between TERT mRNA and albumin. However, a non significant correlation is observed between TERT mRNA and all other studied parameters.
Regarding the comparison between Barcelona A and Barcelona B, TERT mRNA is significantly lower in Barcelona A compared to Barcelona B subgroup. Regarding the comparison between Barcelona A and Barcelona D, AFP and TERT mRNA are significantly higher in Barcelona D compared to Barcelona A subgroup. Regarding the comparison between Barcelona B and Barcelona D, TERT mRNA are significantly higher in Barcelona D compared to Barcelona B subgroup.
Regarding the comparison between Child A versus Child B, INR and TERT mRNA are significantly higher in B compared to A and albumin is significantly lower in Child B versus Child A. Regarding the comparison between Child A and Child C, INR and TERT mRNA is significantly higher in Child C compared to Child A, while albumin is significantly lower in Child C compared to Child A. Regarding the comparison between Child B and Child C, TERT mRNA is significantly higher in Child C compared to Child B and AFP is significantly lower in Child C compared to Child B.
Regarding the diagnostic performance of serum AFP for discrimination between HCC and CLD patients, the best cut-off was 14 IU/mL. This has a diagnostic sensitivity 70%, specificity 60%, PPV 72.4%, NPV 57.1% and efficacy 66%.
On the other hand, the best cut-off value of TERT mRNA for discrimination of HCC from CLD patients was 18(2-ΔΔCT). This has a diagnostic sensitivity 100%, specificity 100%, PPV 100%, NPV 100% and diagnostic efficacy 100%. This proved the superiority of TERT mRNA estimation over AFP in discriminating HCC from CLD.
Regarding the diagnostic performance of AFP for discrimination between HCC and control group, the best cut-off value was 10 IU/mL. This had a diagnostic sensitivity 70%, specificity 80%, PPV 84%, NPV 64% and a diagnostic efficacy 74%.
On the other hand, the best cut-off value of TERT mRNA for discrimination between HCC and control group was 2 (2-ΔΔCT). This had a diagnostic sensitivity 100%, specificity 100%, PPV 100%, NPV 100% and a diagnostic efficacy 100%.
In conclusion, TERT mRNA is proved to be significantly higher in HCC patients compared to CLD patients and control group. Therefore, it can be used as a potential marker for HCC and a complementary diagnostic tool in monitoring CLD patients for detection of HCC. The inclusion of TERT mRNA to the current standard tests for detection of HCC may improve the ability to identify patients who might be missed by current diagnostic strategies and thus might provide a better therapeutic outcome. Moreover, it could distinguish between various Barcelona stages in order to detect the disease at an early stage and hence improve the prognosis and survival rate of the patient.