الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
DLBCL is the most common aggressive type of NHL. It represents approximately 24% of new cases of NHL. In Egypt NHL is the third most common cancer in men and the second most common cancer in women accounting for 10.9% of all cancers in Egypt diagnosed every year. It is heterogeneous disease that can arise de novo or from the histologic transformation and can recognize in clinical presentation and morphology as well as in molecular and cytogenetic studies. DLBCL is defined as a neoplasm of large B-cells arranged in a diffuse pattern.
PIM-2 is a member of serine/threonine proto-oncogenic kinases. PIM-1 and PIM-2 proto-oncogenes were first identified as provirus integration sites for Moloney murine leukemia virus and the resulting overexpression of these kinases leads to lymphoma and leukemia in mice. PIM-2 kinase is frequently overexpressed in human cancer and especially in hematological malignancies where supported malignant cell proliferation and survival.
BMI-1 belongs to the Polycomb group of genes that are important regulators of mammalian lymphopoiesis. Furthermore, BMI-1 has been shown to be essential for self-renewal of hematopoietic and neural stem cells, in part through inhibition of genes regulating senescence.
mi-RNAs are small, single-stranded RNAs that are approximately 22 nucleotides in length. They down-regulate the expression of genes encoding proteins or long non-coding RNAs (lnc-RNAs), by inhibiting mRNA translation or by promoting target RNA degradation. It is estimated that mi-RNAs regulate more than 30% of human protein-coding genes.
miR-RNA BHRF1 is one of two clusters of EBV. It is called BamHI fragment H rightward open reading frame 1. The clusters of this mi-RNA are (ebv-miR-BHRF1-1, ebv-miR-BHRF1-2 and ebv-miR-BHRF1-3). ebv-miR-BHRF1-2 has two type (ebv-miR-BHRF1-2-5p and ebv-miR-BHRF1-2-3p). BHRF1 mi-RNAs have been shown to prevent
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apoptosis in EBV-associated BL by down-regulating caspase-3. Also ebv-miR-BHRF1-3, which down-regulates the chemokine CXCL11 in primary lymphomas.
miR-222-3p is an oncogene that is unregulated in many cancers including HCC, cervical cancer, and gastric carcinoma. miR-222-3p can increase migration and proliferation of tumor cell, and inhibit apoptosis.
miR-26b-5p is a member of miR-26b-5p family . It was found to be in female than in male individuals in the non-tumor liver tissue of hepatocellular carcinoma. Expression of miR-26b-5p was down-regulated in tumors compared with paired noncancerous tissues.
This study aimed to determine the expression of a group of serum mi-RNAs including miR-222-3p, miR-26b-5p, ebv-miR-BHRF1-2-5p and ebv-miR-BHRF1-2-3p and 2 BM oncoproteins including BMI-1 and PIM-2 in DLBCL patients, and correlate the expression status of these markers to the clinicopathological criteria, response to therapy and the survival of the patients.
The study was conducted on 40 serum and BM samples collected from DLBCL patients who admittedto the National Cancer Institute, Cairo University. Samples were collected before any type of treatment. Eighteen serum samples were collected fromage and sex matched healthy vlunteers. The expression levels of miR-222-3p, miR-26b-5p, ebv-miR-BHRF1-2-5p and ebv-miR-BHRF1-2-3p were studied on the serum samples by qRT-PCR using LNA technology, whileBMI-1 and PIM-2 were studied on BM samples using immunohistochemistry technique. Clinicopathological data were collected and the patients were followed up for DFS, PFS, as well as OS. The results of the studied markers were correlated to the clinicopathological and the survival data of the patients and the significance (P values) were determined.
miR-222-3p was up-regulated in 72.5% and down-regulated in 27.5% of patients. miR-26b-5p was up-regulated in 72.5% and down-regulated in 27.5% of patients. ebv-miR-BHRF1-2-3p was up-regulated in 70% and down-regulated in 30% of patients. ebv-miR-BHRF1-2-5p was up-regulated in 62.5%, down-regulated in 15% and normal in 22.5% of patients. BMI-1 was positive expressed in 67.5% and negative expressed in 32.5% of patients. miR-222-3p was up-regulated in 72.5% and down-regulated in 27.5% of patients.
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There was no significant correlation between the expression levels of miR-222-3p, miR-26b-5p, ebv-miR-BHRF1-2-5p and ebv-miR-BHRF1-2-3p,BMI-1 and PIM-2and the clinical pathological characteristics including age, sex, median age, sex, clinical stage, splenomegaly, BM infiltration, reticulin, B symptoms, median LDH, median B2M, HCV, HbsAg and HIV. Regarding the correlation to hematological characteristics, only miR-222-3p, miR-26b-5p and ebv-miR-BHRF1-2-3p had significant correlation to relative lymphocyte/monocyte ratio. In addition, Ebv-miR-BHRF1-2-3p was significantly correlated to Hb level. There was no significant correlation between the markers and metastasis, chemotherapy responsiveness, recurrence or disease progression. Our markers did not show any significant correlation with the survival data including OS, DFS and PFS. However, ebv-miR-BHRF1-2-5p had a near significant correlation to DFS. miR-222-3p, miR-26b-5p and ebv-miR-BHRF1-2-5p were significantly correlated to each other.