Evaluation of miRNA 223/125a and COBLL1 Expressions and ROR-1 Levels as Reliable Markers in B- chronic Lymphocytic Leukemia.

BACKGROUND: miRNA 223 /125a and Cordon-bleu Protein Like 1 (COBLL1) are novel biomarkers that can predict prognosis and guide treatment decisions in patients with chronic lymphocytic leukemia (CLL). Also, there is a growing interest in CLL monitoring based on flow cytometry of receptor tyrosine kinase-like orphan receptor-1 (ROR-1).  Objective: This study aimed to evaluate the relationship between miRNA 223 /125a and COBLL1 expressions and ROR-1 expression in patients with CLL. Also, the study evaluated the relationship between the expression of these biomarkers with tumor staging and cancer progression. METHODS: Our study included 40 patients newly diagnosed with B-CLL. In peripheral blood (PB), miRNA 223/125a and COBLL1 expressions were detected by real-time polymerase chain reaction (real-time PCR) and ROR-1 percentage was detected by flow cytometry before and after treatment.  Results: High level of COBLL1 expression was statistically significantly associated with high ROR-1 percentage expression (P= 0.03). However, a high level of miRNA 223/125a expression was statistically significantly associated with low ROR-1 percentage expression (P=0.002). The sensitivity and specificity of ROR-1 as a predictor of high WBCs count after treatment were 96.6 and 81.1%, respectively. There was a statistically significant reduction of ROR-1 percentage after treatment compared to before treatment (P <0.001). CONCLUSION: ROR-1 percentage expression can be considered a possible prognostic predictor in CLL along with miRNA 223/125a and COBLL1 expressions. This can be explained by the significant correlation between ROR-1 and the studied molecular biomarkers; miRNA 223/125a and COBLL1. In addition, there was a significantly higher ROR-1 percentage in patients with higher WBC counts. Moreover, there was a significant reduction in ROR-1 percentage after treatment.

Peripheral blood CD26 positive leukemic stem cells as a possible diagnostic and prognostic marker in chronic myeloid leukemia.

Background: CD26 is expressed in all chronic myeloid leukemia (CML) patients. This study investigated the role of CD26+ LSCs in diagnosis and follow up of CML patients. Method: Flow cytometry was performed to evaluate CD26+ LSC in peripheral blood (PB) in CML patients. BCR-ABL1 transcript level measurement was performed using standard qRT-PCR technique. Results: CD26+ LSCs were significantly correlated with BCR-ABL1 transcript level at diagnosis and after three months of treatment. CD26+ LSCs also were significantly associated with the risk score after 12 months of treatment. Conclusion: CD26+ LSCs can be a useful marker in diagnosis and follow up of patients with CML.

Association of TNF-α-308 G>A (rs1800629) polymorphism with susceptibility of metabolic syndrome.

BACKGROUND: Metabolic Syndrome (MetS) mainly comprises hyperglycemia, hypertension and dyslipidemia, and has been proven to increase the risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease. Studies have suggested that many factors may be involved in the pathogenesis of MetS, but tumor necrosis factor alpha (TNF- α) may play a strong role as its gene polymorphism was associated with insulin resistance and obesity. The aim of this study was to evaluate the possible association of TNF-α-308 G > A (rs1800629) polymorphism with susceptibility of metabolic syndrome. METHODS: a case-control study was conducted upon 128 participants recruited from Suez Canal University Hospital (Ismailia, Egypt), divided into the MetS group (n = 64) and the control group (n = 64). Genotyping of the TNF-α-308 G > A (rs1800629) polymorphism was performed by restriction fragment length polymorphism (PCR-RFLP). RESULTS: The A allele was significantly higher among MetS patients (40%) than controls (11%) (p < 0.0001). A significant association was observed between the healthy and MetS groups under the influence of co-dominant, dominant and over-dominant genetic models (p < 0.05). Also, there were positive correlations between TNF-α-308 (G/A) polymorphism and risk factors of metabolic syndrome like body mass index (BMI); fasting blood sugar; cholesterol and low density lipoprotein (LDL) (p < 0.05). Regression analysis was done for predictors of MetS and the A allele was found to be a strong predictor (OR 2.752; 95% CI = 1.106 to 6.847; p = 0.03), as well as, BMI; triglyceride (TG); high density lipoprotein (HDL); LDL and cholesterol (p < 0.05). CONCLUSIONS: TNF-α-308 G > A (rs1800629) polymorphism may be play an important role in the development of metabolic syndrome and A allele is a strong predictor in Egyptians.

piRNA-823 Is a Unique Potential Diagnostic Non-Invasive Biomarker in Colorectal Cancer Patients.

Early detection of colorectal cancer (CRC) is the most important factor in deciding its prognosis, so the need to develop an accurate screening test is a must. P-element induced wimpy testis (PIWI) RNA-823 (piR-823) is one of the first piRNAs recognized to be linked to malignancy. We aimed to investigate the expression levels of piR-823 in both serum and tissues of colorectal cancer patients and the ability to use its serum level as a non-invasive diagnostic biomarker to detect colorectal cancer. We determined piR-823 expression levels in 84 serum samples of CRC patients, 75 serum samples of healthy controls, and biological specimens obtained from the 84 patients with colorectal cancer from both the tumor tissues and the normal neighboring tissues using quantitative real-time reverse transcriptase-PCR. We showed that piR-823 had significantly higher serum and tissue expression levels in CRC patients compared to the controls. We observed a significant positive correlation between piR-823 serum levels and the staging of CRC, with significantly higher levels exhibiting advanced stages of CRC (III and IV). This translates into poorer differentiation and lymph node metastasis. The receiver operating characteristic curve (ROC curve) test showed 83.3% sensitivity and 89.3% specificity at a cut-off value of >5.98-fold change, with an area under the curve of 0.933 (p < 0.0001) concerning the ability of piR-823 in diagnosing patients with colorectal carcinoma. piR-823 expression is upregulated in colorectal cancer patients' serum and tissues, and it can be used as a diagnostic noninvasive biomarker for CRC.