carcinoma (HCC) is the sixth most common cancer worldwide, but it ranks as the
second most common cause of cancer-related death worldwide. There has been a
marked increase in HCC-related annual death rates during the past two decades.
Thus, HCC represents a major public health problem.(1).

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Early screening
of patients for HCC has been reported to confer a survival benefit. Patients
who are identified early have multiple treatment options leading to improved

 However, in clinical settings, only
approximately 30% to 40% of patients with HCC can get effective treatment at
the right time, and few molecules have been used as clinical biomarkers for
HCC. Alpha-fetoprotein (AFP), AFP lectin fraction (AFP-L3), and des-?-carboxy
prothrombin (DCP, also known as proteins induced through vitamin K deficiency
or antagonist-II, PIVKA-II) have been used as conventional serum tumor markers,
However, these markers often show false-positive results, and lack sufficient
sensitivity and specificity. (3).

Micro RNAs (MiRNA) are a
special type of short endogenous non-coding RNA with a length of ~22 nt. MiRNAs
are usually regarded as gene repressors at the post-transcriptional level
through binding to the 3?-UTRs of the target mRNAs. (4) . Since many key biological processes including the development,
differentiation, and cell cycles are regulated by microRNAs, the abnormal
expression of microRNAs is often associated with the initialization and progression
of many diseases. Thus, miRNAs usually could serve as suitable biomarkers for
many diseases, such as neurodevelopmental disorders, cancer, and cardiovascular
disease. (5).

The deregulation of specific
miRNAs has been identified in HCC, including miR-148a, miR-203, miR-138, miR-122
and miR-124. Therefore, these miRNAs may become potential therapeutic targets
or candidates for HCC treatment. (6).

In our study, we will
conduct a case control study to evaluate the association between miRNA 196a2
rs11614913 and MiRNA 34 b/c rs4938723 polymorphism with the risk of
hepatocellular carcinoma.



Aim of the

The aim of this work is to
study the expression level of MiRNA 196a2 rs11614913 and MiRNA 34 b/c rs4938723
Gene polymorphism in hepatocellular
carcinoma (HCC) patients using real
time reverse transcriptase polymerase chain reaction (RT-PCR) technique. This will be correlated to
clinical features and laboratory findings at diagnosis.


Review of

1- Hepatocellular

2- Micro RNA.


Subjects and

adult HCC patients will be included in this study, and they will be compare to
40 cirrhotic patients and 20 healthy age- and sex-matched normal controls.

cancer was diagnosed on the basis of at least two imaging methods (ultrasound,
liver CT,) and biochemistry (Alpha fetoprotein AFP).

criteria include patients who previously had: cancer; any metastasized cancer;
radiotherapy or chemotherapy.

All the patients and controls will
be subjected to the following:

1. Full history taking.

2. Clinical examination

3. Laboratory investigations:

· Complete blood count (CBC)

· Liver function test.

·Abdominal ultrasound.

·Alpha fetoprotein(AFP).



·Special Laboratory Investigations:

Study of MiRNA 196a2 rs11614913 and MiRNA 34
b/c rs4938723 Gene polymorphism using real
time reverse transcriptase polymerase chain reaction (RT-PCR) technique




This study will be performed in
compliance with the Helsinki Declaration after approval of the Ethical
Committee of Beni-suef University Hospitals with a written informed consent
will be obtained from all patients. Only patients fulfilling the inclusion
criteria will be included in the study


















1-World Health Organaization. Cancer. Accessed
16 April 2017.


2-Surveillance for hepatocellular carcinoma
is associated with increased survival: Results from a large cohort in the
Netherlands van Meer S, de Man RA,
Coenraad MJ, et al J Hepatol. 2015 Nov; 63(5):1156-63.


3-Alpha-foetoprotein (AFP): A multi-purpose marker in
hepatocellular carcinoma. Sauzay C, Petit A, Bourgeois AM, et al; Clin Chim Acta. 2016 Dec
1; 463():39-44.


4-Hammond, S. M. An overview of microRNAs. Advanced
Drug Delivery Reviews 87, 3 (2015).


5- L. Shen, Y. Lin, Z. Sun, X. Yuan, L. Chen, and B.
“Knowledge-guided bioinformatics model for identifying autism spectrum disorder
diagnostic microrna biomarkers,” Scientific Reports, vol. 6, article
39663, 2016.


Yin W, Zhao Y, Ji YJ, Tong LP, Liu Y, He SX, Wang AQ

Serum/plasma microRNAs as biomarkers for
HBV-related hepatocellular carcinoma in China. Biomed Res Int. 2015;


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