A Clinical Evaluation of Circulating MiR-106a and Raf-1 as Breast Cancer Diagnostic and Prognostic Markers.

OBJECTIVE: MicroRNAs (MiRNAs) regulate mammalian cell growth, differentiation, and apoptosis by altering the expression of other genes and serve multiple roles in tumorigenesis and progression. Proto-oncogene serine/threonine-protein kinase (RAF-1) functions as a part of the MAPK/ERK signal transduction pathway. The present study aim was to prospectively evaluate MicroRNA 106a (MiR-106a) and RAF-1 as a diagnostic and prognostic factor in early prediction of breast cancer (BC), recurrence and early detection of distant metastasis as well as to analyses the statistical correlation between MiR-106a and RAF-1 levels and clinical-pathological parameters including tumor size, lymph node, histological type and grading. METHODS: Sera and plasma of 30 normal women and 50 women with breast carcinoma were assayed for MiR-106a by RT-qPCR as well as levels of Hb, WBCs and platelets count and RAF-1 by solid phase enzyme-linked immunosorbent assay (ELISA). RESULTS: The patients' characteristics, they were classified according to grade into 8% grade I, 66% grade II, 22% grade III and 4% grade IV. The stages were classified according to the TNM system as stage II was the highest percentage 66%, while the lowest percentage was 10% for stage I and 24% for stage III. Also, Hb% and RAF-1 levels were significantly decreased in breast cancer patients as compared with healthy control. On the other hand, MiRNA-106a gene expression was non-significantly increased in positive lymph node metastasis patients (FC=3.66) when compared to patients with negative lymph node metastasis (FC=3.51). In addition, MiR-106a was significantly up-regulated in breast cancer patients with a fold of change 3.63 when compared to control samples. CONCLUSION: Expression of MiR-106a gene can be used as a diagnostic and prognostic noninvasive biomarker which can stimulates breast cancer cell invasion and proliferation through downregulation of Raf-1 levels.
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Clinical Potentials of miR-576-3p, miR-613, NDRG2 and YKL40 in Colorectal Cancer Patients.

INTRODUCTION: Colorectal cancer (CRC) is the most common type of gastrointestinal tract cancers. This investigation aim was to assess the expression of miR-576-3p and miR-613 in CRC patients in addition to NDRG2 and YKL40 serum levels determination to decide their diagnostic and prognostic significance. METHODS: Sixty early diagnosed CRC patients prior to any treatment in addition to twelve healthy subjects were enrolled in this study. Blood samples were taken from subjects and allowed for clotting and centrifugation, then the collected sera were stored at -80ºC till it were used for detection of our molecular biomarkers. The mature miRNAs expressions (miR-576-3p and miR-613) were detected in serum by qRT-PCR, while NDRG2 and YKL40 serum levels were determined by ELISA. In addition, the correlation of the measured parameters with the clinicopathological data of the patients was investigated. RESULTS: The study results showed that both miRNA-576-3p and miRNA-613 were down-regulated in CRC patients with fold change 0.33, 0.36; respectively. A significant positive correlation was observed between miR-576-3p and miR-613 (r = 0.75, p < 0.001). NDRG2 serum levels were decreased in patients compared to the control group but the decrease wasn't statistically significant. On the other hand, it was observed that YKL40 serum level was significantly increased in CRC patients compared to control (p-value < 0.001). Furthermore, YKL40 showed a very high diagnostic value (AUC = 0.97, specificity = 91.7%, sensitivity = 96%, p-value = 0.0001). CONCLUSION: The observations of this investigation concluded that, the expressions of miR-576-3p and miR-613 in addition to YKL40 serum levels determinations may help in the diagnosis of CRC.

Expression and clinical significance of SNAI1 and ZEB1 genes in acute myeloid leukemia patients.

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults, it represents nearly 32% of all new cases of leukemia. This study aimed to evaluate the SNAI1 and ZEB1 genes expression in AML patients and determine their diagnostic and prognostic significance. We determined the expression of SNAI1 and ZEB1 genes and serum E-cadherin levels in early diagnosed patients with AML. Sixty early diagnosed AML patients and 20 healthy subjects were enrolled in this study, SNAI1 and ZEB1 genes expression was determined by Real-time PCR while E-Cadherin serum levels were determined by ELISA. The results of this study demonstrated that, all AML patients positively expressed the SNAI1 gene with fold change 2.6. While, the ZEB1 expression was positive in 56.7% of the patients with fold change 1.8. SNAI1 and ZEB1 genes were highly expressed in M5 subtype (FC = 13.8 and 9.3, respectively). On the other hand, serum E-cadherin concentrations of the AML patients showed decrease when compared with those of the control but the decrease was not reach to the significance level. The findings of this study suggest inclusion of SNAI1 and ZEB1 genes expression in the cluster of potential genetic biomarkers to be studied in AML cases as diagnostic and prognostic markers.