الملخص الإنجليزي
Epithelial Ovarian Cancer (EOC) is the most lethal disease among gynecologic cancers. It is usually diagnosed at late stages with a poor outcome due to its asymptomatic nature. Statistical estimations revealed around 14,080 deaths out of 22,440, diagnosis in the United States only in 2017, in which less than 40% of women are cured. In Oman, incidence rate of ovarian cancer in 2013 is estimated at 2.2, and 2.9 after age- standardization, per 100,000. Despite the tremendous research effort achieved in this field, genetic mechanisms associated with this disease are still not fully understood. Recently, several biological techniques including microarray, chromatin immunoprecipitation (ChIP) and others, emerged to reveal a bunch of genes with a potential of biomarkers in cancerous cells as compared to normal cells. However, there is no concrete evidence that those biomarkers have a role in the progression and/or early detection of the disease. Therefore, biomarkers for an early-detection of patients at higher risk to develop EOC are urgently needed. In a previous work, we used chromatin immunoprecipitation (ChIP) technique to study the E2F5 transcription factor in ovarian cancer cell line (MCAS and OVSAHO). A mini library was obtained by the enriched chromatin and ChIP-seq was performed to identify the sequences of downstream regulatory elements bounded by E2F5. Among the short-listed genes, SOCS-2 was found to be regulated by the E2F5 gene. Suppressor of Cytokine Signaling 2 (SOCS2) is one of the SOCS family with a role in JAK/STAT transcription pathway. Any disruption in this pathway may lead to many diseases such as immunity disorders and some sort of cancers. Some of these SOCS genes have been suggested to act as biomarker for some cancers. SOCS2 was recently shown to act as an early biomarker for prostate and colorectal cancer. The aim of this study is to explore the role of SOCS2 gene in Epithelial Ovarian Cancer by monitoring the expression of the gene in stages variety of EOC tissues and cell lines. We examined the expression of SOCS2 in tissues and cell lines using the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to monitor the differential expression of SOCS2 in cancerous and normal tissues. Significant down-regulation of SOCS2 was found in Borderline tissues but it was not significant in other cancer stages such as benign and malignant tissues. Although all examined cell lines (MCAS, OVSAHO and 2008OV) showed a significant downregulation of the gene. SOCS2 methylation status was investigated in tissues and cell lines using MSP. It was revealed that SOCS2 is methylated in OVSAHO cell line but no methylation was detected in MCAS. Cancerous tissues showed partially methylated SOCS2 as well as normal tissues. In conclusion, this study manifested that SOCS2 gene is downregulated at an early stage of EOC. Also, the low expression of the gene could be due to another mechanism rather than hypermethylation of the gene.
