الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Lung cancer is now the second most common cancer between men and women. Lung cancer is classified histologically into two principal types; small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC represents 85% of lung cancer cases. It is sub classified into adenocarcinoma, squamous cell carcinoma and other rare types.
Risk factors for lung cancer mainly include smoking, exposure to second-hand smoking, environmental factors as exposure to asbestos, radon gas or other carcinogens and genetic factors. These factors differ in their influence depending on age, sex, race, and synergistic interaction. Genomic wide association studies had identified common genetic variations associated with the pathogenesis of lung cancer. They investigated up to one million single nucleotide polymorphisms, but they only contribute to less than 10% of cancer risk.
Several genetic and epigenetic mechanisms can affect the development of lung cancer. HOXA9 gene is a tumor suppressor gene whose promoter hypermethylation leads to transcriptional inactivation. Its low expression is associated with EMT and may be characteristic of tumor aggression in NSCLC patients. Copy number variation is a one of the genetic mechanisms responsible for malignant transformation. CNV can affect several signaling pathways as those controlling cell proliferation and apoptosis as SOX2 gene or oxidative phosphorylation as HV2 gene. Dysregulation of SOX2 expression has been linked to cancer pathogenesis through its role in induction of cellular proliferation mediated by EGFR gene activation, EMT, migration, invasion, metastasis and resistance to apoptosis.
So, this study aimed to determine the association of SOX2 and HV2 genes copy number variation and HOXA9 gene promoter methylation in cfDNA with NSCLC in the Egyptian population. This study included twenty five Egyptian patients selected from Chest Diseases Department at Alexandria Main University Hospital, having NSCLC which was confirmed by histopathological examination of lung biopsy, whose age ranged from 30 to 75 years with a mean 59 years, including 92% males and 8% females. Patients who had history of previous cancer, chronic or systemic diseases, undergone tumor surgical resection or received chemotherapy and radiotherapy were excluded from the study. Twenty five healthy individuals, whose age ranged from 34 to 78 years with a mean 53.40 years, including 92% males and 8% females with no history of previous cancer were included as a control group.
Three milliliters of blood were collected in a plain tube, and used for assessment of ALT, AST, BUN and creatinine. Two mL of whole blood were collected in K3 EDTA and used for performing CBC. Another two mL of whole blood were withdrawn in K3 EDTA tubes. Samples were transferred to the lab immediately to be used for circulating free DNA (cfDNA) isolation. Once isolated, plasma samples were transferred into clean 2-mL tubes and freezed at -80°C until time of handling.