Potential value of circulatory microRNA122 gene expression as a prognostic and metastatic prediction marker for breast cancer.

Despite progress in terms of management, breast cancer still constitutes a major threat to health worldwide. Various microRNAs have been shown to play a fundamental role in tumor biology during development and progression. Therefore, our study was focused on investigating the role of circulating microRNA122 (miR-122) in breast cancer and its clinical utility as a potential easily accessible biomarker for use in the diagnostic and prognostic assessment of breast cancer. Determination of the serum CA15-3 and carcinoembryonic antigen levels was conducted using an enzyme-linked immunosorbent assay. The expression level of miR-122 was determined using real time PCR in 90 breast cancer patients and 60 healthy controls. Higher circulating miR-122 levels were found in breast cancer patients than in controls and higher miR-122 levels were observed in patients who experienced metastasis. Additionally, miR-122, at a cutoff > 2.2, had a sensitivity of 93.33% and a specificity of 90% when used to distinguish breast cancer patients from controls and was able to predict metastasis at a cutoff > 10.9 with a sensitivity of 95.83% and a specificity of 65.15%. Kaplan-Meier survival analysis revealed that high miR-122 expression is significantly associated with decreased overall survival and progression-free survival. This study concludes that circulatory miR-122 could be utilized as a diagnostic and prognostic biomarker in breast cancer patients.

Serum circulating cell free DNA as potential diagnostic and prognostic biomarker in non small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is leading cause of cancer related death and the survival rate for patients with NSCLC remain poor so early diagnosis of NSCLC represents the best opportunity for cure. Cell-free DNA (cf-DNA) is extracellular nucleic acids found in cell-free plasma/serum of humans, given the recent approval of a liquid biopsy in lung cancer, the use of circulating tumor DNA as a novel non-invasive diagnostic and prognostic biomarker is promising. OBJECTIVES: Studying whether the concentrations of circulating Cell Free DNA in serum can be used as a diagnostic and prognostic biomarker for NSCLC patients. METHOD: This study was carried out on 140 subjects included 60 patients with non small cell lung cancer,40 patients with Chronic Obstructive Pulmonary Disease (COPD) and 40 healthy controls. Quantitative analysis of serum circulating cf-DNA was done b y AlU-based quantitative real time PCR. Serum level of CEA was measured by ELISA. RESULTS: NSCLC patients demonstrated significantly higher values of each of ALU 215, ALU 247, and DNA integrity than both COPD patients and controls. On ROC curve analysis, the total accuracy of ALU 247, ALU 115, DNA integrity (92.1%, 83.6%, 56.4%) at cutoff points (325, 565 & 0.48) respectively. On combining both DNA integrity and CEA, improved sensitivity to 93.3% was noted. For NSCLC patients, ALU 115 & ALU 247 increased significantly with more advanced stage and highest level was noticed in metastatic patients. Regarding survival there was better overall survival among patients with low DNA integrity. CONCLUSION: Serum cf-DNA concentrations and integrity index may be valuable tool in early diagnosis of NSCLC and prediction of prognosis of those patients.

Clinical study of Presepsin and Pentraxin3 in critically ill children.

PURPOSE: To assess the value of Presepsin and Pentraxin3 measurement in critically ill children. MATERIALS AND METHODS: Prospective observational study conducted on 80 children admitted into Pediatric Intensive Care Unit (PICU) and 80 healthy controls. Patients were evaluated for presence of sepsis. Pediatric Risk of Mortality (PRISM) and Pediatric Index of Mortality (PIM2) were calculated. Serum Presepsin and Pentraxin3 were measured within 24 h of admission. RESULTS: Presepsin and Pentraxin3 were significantly higher among the whole patient cohort and among septic patients compared with controls (p < 0.001) but no difference was found between septic and non-septic patients. Pentraxin3, but not Presepsin, was significantly higher among non-survivors compared with survivors (p = 0.048) and was correlated with PIM2. Receiver operating characteristic (ROC) curve analysis revealed that Pentraxin3 had an AUC of 0.631 for prediction of mortality which was comparable to that of PRISM and PIM2. Presepsin was associated with a higher rate of mechanical ventilation and longer PICU stay. CONCLUSIONS: Presepsin and Pentraxin3 are acute phase proteins potentially useful for monitoring critically ill children and diagnosing sepsis. Pentraxin3 is associated with mortality but modestly discriminates survivors from non-survivors. Presepsin is associated with certain indicators of disease severity. Larger studies are certainly required.

Cytokine Gene Polymorphism in Children With Idiopathic Nephrotic Syndrome.

INTRODUCTION: Idiopathic nephrotic syndrome (INS) is a glomerular disease with completely unclear pathogenesis and different responses to steroid therapy. This study aimed to investigate the role of cytokine genes promoter polymorphisms in steroid therapy responses. MATERIALS AND METHODS: One hundred children with INS and 30 healthy controls were studied. Genotyping of TNF-α-G308A single nucleotide polymorphism was done using polymerase chain reaction-restriction fragment length polymorphism method, while of IL-6-G174C single nucleotide polymorphism was done using real-time polymerase chain reaction. RESULTS: The IL-6-G174C exhibited a significantly different genotype distribution among the children with INS compared with the controls (GG versus CC, P = .02; GG versus GC, P = .003; odds ratio [OR], 5.83; 95% confidence interval [CI], 1.64 to 20.70; as well as alleles distribution of G versus C, P ? .001; OR, 7.57; 95% CI, 2.28 to 25.17). With regard to TNF-α-G308A genotype, there was no significant difference in genotype distribution of the children with INS compared with the controls, but a significant difference was observed at the alleles level. Comparing the steroid-resistant group with the steroid-sensitive group, significant association was found at genotypic level in case of IL-6-G174C (GG versus CC, P = .03; OR, 5.52; 95% CI, 1.39 to 21.89), but no association was found regarding GG versus GC. At the allelic level of IL-6-G174C, there was no significant association either. CONCLUSIONS: IL-6-G174C and TNFα-G308A polymorphisms may affect susceptibility to idiopathic nephrotic syndrome and might affect steroid response in INS patients.

Association of endothelial nitric oxide synthase (eNOS) gene G894T polymorphism with hypertension risk and complications.

This study evaluated the association of NOS3 polymorphisms with hypertension risk and complications. eNOS (G894T) SNP was performed by RT-PCR on 70 hypertensive patients (25 were hypertensive, 25 were hypertensive with CAD, and 20 were diabetic with hypertension) and 30 age- and gender-matched individuals. Lipid and glucose profile were assessed by standard colorimetric assay. Our results revealed that combination of (GT + TT) genotype and T allele significantly increases the risk of hypertension (OR = 3.86 and 4.33), respectively. Subgroup analysis showed significant association between CAD with eNOS (G894T) mutant genotype (P = 0.002) and allele frequency (P < 0.001). Moreover, the mutant homozygous and heterozygous eNOS genotype together were significantly associated with higher TC, LDLc, (P < 0.001), and TG (P = 0.001). Thus, hypercholesterolemia (P < 0.001 and OR = 12.48) increases the risk of hypertension among T carrier. These results indicated that the T carriers significantly increase hypertension risk and complication (CAD), mainly with hypercholesterolemia and in elderly.

The potential implication of SCN1A and CYP3A5 genetic variants on antiepileptic drug resistance among Egyptian epileptic children.

PURPOSE: Despite the advances in the pharmacological treatment of epilepsy, pharmacoresistance still remains challenging. Understanding of the pharmacogenetic causes is critical to predict drug response hence providing a basis for personalized medications. Genetic alteration in activity of drug target and drug metabolizing proteins could explain the development of pharmacoresistant epilepsy. So the aim of this study was to explore whether SCN1A c.3184 A/G (rs2298771) and CYP3A5*3 (rs776746) polymorphisms could serve as genetic based biomarkers to predict pharmacoresistance among Egyptian epileptic children. METHODS: Genotyping of SCN1A c.3184 A/G and CYP3A5*3 polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed in 65 healthy control subjects and 130 patients with epilepsy, of whom 50 were drug resistant and 80 were drug responsive. RESULTS: There was a significant higher frequency of the AG genotype (p=0.001) and G allele (p=0.006) of SCN1A polymorphism in epileptic patients than in controls. Also their frequency was significantly higher in drug resistant patients in comparison with drug responders (p=0.005 and 0.054 respectively). No significant association between CYP3A5*3 polymorphism and drug-resistance was found. CONCLUSIONS: Overall, results confirmed the claimed role of SCN1A c.3184 A/G polymorphism in epilepsy and moreover in development of pharmacoresistance among Egyptian epileptic children. CYP3A5*3 variants have no contributing effect on pharmacoresistance among Egyptian epileptic children.