الفهرس 
HEPATOCELLULAR CARCINOMAOnly 14 pages are availabe for public view
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Abstract
Hepatocellular carcinoma (HCC) is the most common
primary liver cancer. The mortality of liver cancer worldwide is
ranked as fourth between other cancer causes in males and
females. In Egypt, it is a major problem due to the high
prevalence of Hepatitis C Virus infection.
The occurrence and progression of HCC depends on
many risk factors, but the main and most important risk is liver
cirrhosis of any cause followed by hepatitis B, C, obesity, Nonalcoholic
fatty liver disease (NAFLD) and aflatoxin.
The surveillance programs and diagnostic testing
modalities for HCC in all guidelines depends on the
radiological methods. The main serum biomarker used
nowadays is the AFP although it has unfavorable sensitivity
and specificity and its role is limited to screening. These were
the main reasons that led researchers to look for new modalities
of testing to diagnose HCC in early stages where radical
treatment options can take the upper hand.
MicroRNAs are considered from the short non-coding
RNAs. It can control the genetic material by affecting the
mRNA of the gene at the post-transcriptional level or even
affect the gene itself at the transcriptional level. It was also
discovered that microRNA can stimulate (up-regulate) or
inhibit (down-regulate) the target genes.In addition, microRNA was found to have a great role
and can be used in diagnosis of many tumors giving the chance
for early non-invasive diagnostic methods.
In this study, our aim was to characterize the expression
of the serum non-coding microRNA (miR-519d-3p) and the
associated targeted gene SQSTM1 to evaluate their usefulness
as diagnostic molecular biomarkers for HCC.
This study was conducted at Internal Medicine
Department, Faculty of Medicine, Ain Shams University and it
was approved by the Ethical Committee of Ain Shams
University, Faculty of medicine.
The study included (50) participants from the Internal
Medicine Department, Hepatology Unit, inpatients wards &
outpatient clinic, divided into (34) HCC patients diagnosed
according to American Association for the Study of Liver
Diseases (AASLD) practice guidelines using multiphasic
contrast-enhanced CT imaging, (11) chronic liver infection
patients and (5) normal volunteers.
All subjects enrolled in the study were subjected to
detailed history taking, full physical examination, laboratory
investigations, including serum ALT, AST, serum albumin,
serum bilirubin Total, direct, INR, viral markers as (HCV Ab,
HBVs Ag) serum AFP and imaging studies which included
pelvi-abdominal ultrasonography and triphasic contrastenhanced CT imaging. In addition, quantitative real time
polymerase chain reaction (qRT-PCR) were conducted on
serum samples to detect the level and pattern for the microRNA
(hsa-miR-519d-3p) and the mRNA of (SQSTM1) gene in HCC
cases with or without hepatitis virus infections and compare it
with the level in chronic liver infected cases and also with
healthy personnel. All data were statistically analyzed. Results
were compared to results of similar researches.
Our results showed that the serum level of miRNA (hsamiR-
519d-3p) is upregulated in the serum of Hepatocellular
group in comparison with chronic liver infection group and the
healthy group. These results were also seen with the serum
level of mRNA (SQSTM1), as a significant upregulation of its
serum level were detected in HCC group compared to the levels
in chronic liver infection and healthy groups.
In addition to these results, the sensitivity and specificity
of (hsa-mir-519d-3p), (mRNA of SQSTM1) in comparison to
(AFP) was (91.2%-81.8%), (97.1%-100%) and (76.5%-72.7%)
respectively. And the best cut off values of the three tests was
(≥ 8.34) for miR-519d, (≥ 7.89) for mRNA SQSTM1 and
(≥7.30) for AFP.
All these results showed that the serum microRNA (miR-
519d) and the messenger RNA of (SQSTM1) gene as
diagnostic tests of HCC, showed higher sensitivity andspecificity than that of AFP, and accordingly it can be used in
detecting early cases of HCC with better results.
In addition, we have identified that (hsa-mir-519d-3p)
has upregulated its targeted gene (SQSTM1) and this
upregulation is at the transcriptional level not at the post
transcriptional level as it increased the mRNA level. This
action of (mir-519d-3p) on SQSTM1 gene go with their actions
as oncogenic microRNA and oncogenic gene in the progression
of HCC.