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العنوان
Programmed Death-Ligand 1 (PD-L1) Gene Polymorphisms as Predictive Markers for Development of Hepatocellular Carcinoma in chronic Hepatitis C Virus Patients /
المؤلف
Attia, Mohammed Saad.
هيئة الاعداد
باحث / محمد سعد عطيه محمد
مشرف / زينب احمد على الدين
مشرف / جمال العطار
مشرف / هانى هارون قيصر
مشرف / أميرة اسحاق سمعان
مشرف / مروة حسن
تاريخ النشر
2020.
عدد الصفحات
161 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
طب الجهاز الهضمي
تاريخ الإجازة
1/1/2020
مكان الإجازة
جامعة عين شمس - كلية الطب - الباطنة العامة والجهاز الهضمي والكبد
الفهرس
Only 14 pages are availabe for public view

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Abstract

Hepatocellular carcinoma is the sixth most common cause of cancer, and ranks fourth among the causes of cancer-related death.
Major risk factors for HCC include chronic alcohol consumption, hepatitis B, hepatitis C and non-alcoholic fatty liver disease. Tumor progression is a complex disease process involving various factors, changes of various genes, and the development of multiple stages.
Programmed dealth-1 (PD-1) is an immune checkpoint receptor that is up regulated on activated T cells to promote tolerance to self-antigens and limit immune-based pathological damage, Engagement of PD-1 with its ligand-1 (PD-L1) antagonizes the co-stimulatory signals and leads to the blockade of T cell activation.
A common type of genetic variation in the genome was single nucleotide polymorphism (SNP). PD-L1 have multiple SNPs To evaluate the relevance of PD-L1 SNPs in terms of the risk of HCC, (rs4143815 and rs2297136) SNPs were selected for examination in this case-control study for providing a genetic marker to predict cancer risk and development.
This study was conducted in co-operation between Gastroenterology and Hepatology Department, Ain-Shams University and the Gastroenterology and Hepatology Department, Theodor Bilharz Research Institute “between” March 2020 to July 2020. It included total participants of 138 Divided into three groups:
o First Group: Thirty five normal populations.
o Second Group: Fifty one patients with liver cirrhosis.
o Third group: Fifty two patients with liver cirrhosis and HCC.
The patients were recruited from the Hepatology department of Theodor Bilharz Research Institute Hospital.
All patients were subjected to; full history taking, thorough clinical examination, laboratory and radiological investigations including Genotyping:
Genomic DNA extraction
PD-L1 gene polymorphisms (rs4143815and rs2297136) detection by real time PCR using Taqman SNP genotyping assay.
Our study demonstrated that there are two gene polymorphism showed significant increase in cirrhosis group vs. control rs2297136 (AA) (46.6%) vs. (14.3%). and rs4143815 (GG) (42.1%) vs. (25.3%) respectively also they showed significant increase vs. HCC group.
Also, the present study demonstrated that the functional polymorphisms (rs4143815) (CG) of the PD-L1 gene were associated with HCC risk as it is expressed in (51.3%) in HCC, (25.6%) in cirrhosis and (23.1%) in control group.
There is significant increase in rs4143815 (CG) with age as 95% of gene positive patients more than 50 years.
And, rs4143815 (CG) show significant increase in Child C patients as (75%) Child C vs. (10%) Child A and (45%) was MELD/NA (20-29) vs. (10%) <9 with (70%) of patients were stage D in BCLC and statistically significant association of three genes with single HCC more than 3cm.
So, PDL-1 gene polymorphism rs4143815 (CG) could be used as a predictive marker for HCC after validation by larger studies or met analysis.