Thesis (Ph.D.) - Cairo University - National Cancer Institute - Department of Clinical Pathology

Background: Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies and leading causes of cancer related deaths all over the world. MicroRNAs can regulate more than 60% of human genes, including oncogenes and tumor suppressor genes. Therefore, they can promote tumor development and affect risk of malignancy. The abnormal high expression of the oncogenic microRNA, miR-92a in colorectal cancer promotes tumor proliferation, metastasis, and invasion via targeting and inhibiting different tumor apoptosis proteins including the anti-apoptotic molecule BCL-2-interacting mediator of cell death (Bim).Aim of the work: This study aimed to assess the role of serum miR-92a as a non-invasive tumor marker in clolorectal cancer (CRC) patients, outline the correlation between miR-92a and the pro-apoptotic protein BCL-2-interacting mediator of cell death (Bim) as one of its target proteins, and to determine their associative relations with other clinicopathological parameters in CRC and adenoma patients.Materials and Methods: A total of 54 newly diagnosed CRC patients,15 colonic adenoma patients, and 15 age-matched apparently healthy volunteering controls were recruited in this study. MiR-92a levels were assayed by TaqMan- Real time RT-PCR method and Bim levels were measured by ELISA. Results: Significant higher expression of serum miR-92a levels were observed in CRC patients as compared to the adenoma and control groups (p <0.001 each) and lower serum Bim levels in CRC patients as compared to the adenoma and control groups (p=0.001, p <0.001 respectively).The ROC curve analysis showed excellent AUC for plasma miR-92a in discriminating CRC from control (AUC=0.994), and adenoma (AUC=0.993) groups with the highest diagnostic performance in discriminating CRC from control (at cut off 1.43, sensitivity 98.1%, specificity 93.9%), and adenoma (at cut off 1.78, sensitivity 92.6%, specificity 93.3%)

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