الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 201 |  |  |
| | | from | 201 | | |
Abstract
Hepatocellular Carcinoma (HCC) represents the fifth most common cancer in the world and the second most frequent cause of mortality among oncological patients. It is responsible for 500,000 deaths globally every year. It represents the most common primary malignant tumor of the liver, Its incidence is increasing because of hepatitis B and C virus infections. Egypt has the highest prevalence of HCV in the world with 13.8% of the population infected and seven million with chronic HCV liver disease. Up to 90% of HCC cases in the Egyptian population were attributed to HCV.
Early detection of HCC opens doors for various effective treatments such as surgical resection, radiofrequency ablation, and transplantation, which can subsequently lead to long-term survivals in a great number of HCC patients. Early detection is possible with ultrasound scanning and AFP monitoring, although the use of AFP as a screening test is complicated by frequent false positive and false negative results. In addition, AFP serum concentrations do not correlate well with the prognostic parameters of HCC such as tumor size, stage, or disease progression. Ethnic variability may also exist. Furthermotare, in some cases of HCC, AFP elevations are not apparent at all. Besides, serum AFP levels are frequently not elevated at a significant proportion in patients with early-stage potentially curable HCC. Therefore, other markers should be studied in an attempt to identify a more sensitive laboratory test.
Several lines of evidence have suggested that lncRNAs are biologically functional rather than transcriptional “noise”. The mechanisms through which they act are molecular scaffolds, which are involved in transcriptional machinery, as post-transcriptional regulators of splicing or as molecular decoys for miRNA.
lncRNA-TSIX plays oncogenic roles in tumor growth and metastasis, and it may act as a potential biomarker and therapeutic target for human cancers.As It is upregulated in several cancers, It is a novel long non-coding RNA acts as a crucial effectors in several cancers.
In this regards, we evaluate the clinical utility of serum levels of lncRNA-TSIX and miRNA 548 AND SOGA mRNA expression as a non invasive biomarkers in diagnosis of HCC and to correlate their expression with different clinicopathological factors.
This study was done at Medical Biochemistry Department, Faculty of Medicine, Ain Sham University during the period from November 2015 – September 2016 and included 53 patients and 17 normal volunteers attended from Ain Shams University Hospitals.
The aim of the current study was to evaluate the clinical utility of serum levels of lncRNA-TSIX and miRNA-548 and SOGA mRNA expression as a non invasive biomarkers in diagnosis of HCC by quantitaive Real Time -PCR and to correlate the expression of them with the various clinico-pathological parameters in an attempt to evaluate their role in tumor assessment and to explore their synergistic expression and their use as potential selected diagnostic biomarkers.
The studied individuals were classified into three main groups:
group 1, including 35 malignant cases of hepatocellular carcinoma median age was 58 years.
group 2, including 18 hepatitis c virus chronic individuals median age was 54 years
Group3, including 17 healthy normal individuals median age was 48 years
All studied subjects were subjected to Full clinical examination and radiological examinations preceded by complete history taking and routine laboratory investigations including liver function tests as serum ALT, serum AST, serum albumin, prothrombin time and serum total bilirubin, serum AFP . Evaluation of lncRNA-TSIX, miRNA-548 and mRNA SOGA expression in serum samples was performed by real time PCR in relation to ACTB as a housekeeping internal control for SOGA and LncRNA TSIX and RNU-6 as a housekeeping for miR-548.
Then the results were calculated and statistically analyzed by the SPS software.
A significant difference was observed in the Positivity rate of lncRNA-TSIX, miRNA-548 and mRNA SOGA in serum samples of the malignant group i.e. (80%, 80%,82.9%) as compared with both CHC group (22.2%,11.1%,11.1%) and healthy normal group (11.8%,11.8%,17.6%) respectively (P= 0.000).
Applying (2.65,7.65, 1.4), as a cut off value; which was calculated by ROC curve, the lncRNA-TSIX and miRNA-548 and mRNA SOGA showed (80%,80%,82.9%) sensitivity, (82.9%,88.6%,85.7%) specificity, (82.35%,73.68 %,85.33 %) PPV, (80.5 %,96.9 %,83.319 %) NPV and (81.45 %,84.3 %,84.3 %) accuracy.
Supported our previous hypothesis that the lncRNA-TSIX , miRNA-548 and mRNA SOGA may play an important role in early detection of HCC. And could be used as a non invasive biomarkers in combination with AFP to improve the sensitivity of HCC diagnosis.
A highly significant correlation found between the three groups as regard fold change of serum lncRNA-TSIX and fold change of serum miRNA-548 and mRNA SOGA which may indicat their synergestic effect.