الفهرس 
Introduction & Aim of the workOnly 14 pages are availabe for public view
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Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer
worldwide and is associated with liver cirrhosis (LC) in 80% of cases.
miRNAs are approximately 22-nucleotide, noncoding, endogenous
RNA molecules with an important role in a number of biological
processes, including embryonic development, cell differentiation, and
tumorigenesis.
Recently, many studies suggest a link between aberrant expression
of miRNAs and various cancers including HCC, recent studies have
documented the involvement of miRNAs in HCC in tumor progression
and metastasis.
miRNA- 21 is one of the first miRNAs to be described as
an oncomir as most of the targets of miRNA-21 are tumor suppressors
such as Phosphatase and tensin homolog (PTEN), programed cell death
4 (PDCD4), Tropomyosin and others. It is upregulated in many types of
human cancers.
PDCD4 is a tumor suppressor gene that plays an important role in
regulating apoptosis, invasion and metastasis.Several reports described
the regulation of PDCD4 by miRNA-21.
So this study aimed to evaluate the diagnostic potential of
circulating miRNA-21 and study its effect on programed cell death 4
(PDCD4) gene expression in Egyptian patients with HCC.
The present study was conducted by collaboration between
Medical Biochemistry Department, Faculty of Medicine, Clinical
Biochemistry and Oncology Departments, National Liver Institute,
Menoufia University. It included 70 subjects: 30 patients with HCC, 20 patients with CLD secondary to HCV infection presented to the inpatient
wards and outpatient clinic of Oncology Department, National Liver
Institute, Menoufia University in the period from January 2014 to
December 2014, and 20 unrelated apparently healthy subjects matching
age and gender served as control group.
All patients and control groups were subjected to the following:
1. Complete history taking.
2. Complete clinical examination.
3. Abdominal ultrasonography and/ or CT.
4. Laboratory investigations including: complete blood picture, liver
function tests, viral markers (HBsAg, HCV-Ab), estimation of
serum AFP and molecular testing for miRNA-21 expression and
PDCD4 gene expression.
The results of this study revealed the following:
The groups were homogenous regarding age and gender.
There was no significant difference between HCC and CLD groups
regarding all studied variables (liver function tests and AFP) except
ALP, GGT and AFP which showed significant increase in HCC
group.
There was significant decrease in hematological indices (Hb –
RBCs – platelet count) in both HCC and CLD groups compared to
control group. Meanwhile, no significant difference was detected
between HCC and CLD groups.
There was significant increase of miRNA-21 in HCC group
compared to each of CLD and control groups. However, it showed
no significant difference between CLD and control groups. PDCD4
gene expression showed significant decrease in HCC group compared to each of CLD and control groups. Meanwhile, it
showed no significant difference between CLD and control groups.
There was significant inverse correlation between miRNA-21and
PDCD4 gene expression RQs in HCC group.
There was significant positive correlation between miRNA-21 and
AFP and significant inverse correlation between PDCD4 and each
of total and direct bilirubin in HCC group. A significant positive
correlation was detected between miRNA-21 and ALT as well as
between PDCD4 gene expression and GGT in CLD group.
Meanwhile, No significant correlation was detected between
miRNA-21 and PDCD4 gene expression and all studied parameters
in control group.
The mean RQ of miRNA-21 showed significant increase, with
presence of cirrhosis, increased number of focal lesions, larger size
of tumor, advanced tumor stage and presence of vascular invasion.
Meanwhile, the mean RQ of PDCD4 gene expression showed a
significant decrease with increased number of focal lesions, larger
sized tumors and and advanced stages of HCC. However, no
significant difference in serum AFP was detected regarding the
aforementioned variables.
The mean RQ of circulating miRNA-21 and the mean serum level
of AFP showed a highly significant elevation in HCC patients with
early tumor development (single focal lesion, tumor size <3cm, and
collectively TNM 1 and 2 stages) compared to each of the control
and CLD patients groups, while no statistical difference was
detected regarding the mean RQ of circulating PDCD4 gene
expression.
Receiver Operator of characteristics (ROC) curve analysis of AFP
and miRNA-21: displayed that the best cut-off of serum AFP for
differentiation of HCC cases from those without HCC was 91.7
ng/ml, at this cut-off; the sensitivity, specificity, PPV, NPV and
overall accuracy were 75.2 %, 92.3 %, 90.2 %, 69.2%, and 77.0 %
respectively. For miRNA-21 the best cutoff was 3.93 RQ with
sensitivity, specificity, PPV, NPV and overall accuracy of 90 %,
94.8 %, 94.4 %, 87.5 % and 92.5 % respectively. Combined use of
two parameters was superior to the use of AFP alone as the
sensitivity, specificity, PPV, NPV and overall Accuracy were
91.3%, 97%, 96%, 90% and 92% respectively.