Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1): A molecular predictor of poor survival in glioblastoma multiforme in Egyptian patients

Background: Long noncoding RNAs (lncRNAs) are a recently discovered class of transcribed RNA molecules with a length of more than 200 nucleotides. Recent studies have shown that lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) could play an important role in carcinogenesis and cancer progression in several types of malignancies.Objective: As little is known about the role and clinical significance of lncRNA MALAT1 in glioblastoma multiform (GBM) patients in Egyptian population, this study aimed to investigate the expressions of lncRNA-MALAT1 in human GBM samples and to correlate these expressions with the available clinicopathological features including patient survival data.Subjects and methods: The relative expression of MALAT1 was determined in 37 human glioblastoma formalin-fixed paraffin embedded (FFPE) tissue samples and 10 FFPE non-neoplastic brain tissues using quantitative reverse transcription polymerase chain reaction (qRT-PCR) technology.Results: The current results revealed that lncRNA MALAT1 expression was down-regulated in all tumor specimens compared to normal tissues. A receiver operating characteristic (ROC) curve analysis showed high diagnostic performance; area under curve (AUC) =0.925 ± 0.038 (P <0.001), 95% CI= 0.850–1.00, with 94.6% sensitivity, and 72.7% specificity. Lower MALAT1 expression was associated with poor prognosis; higher frequency of recurrence (P < 0.044), lower overall survival (P <0.005), and shorter disease-free survival (P < 0.004).Conclusion: Taken together, we could postulate that MALAT1 might have a tumor-suppressive function in GBM in Egyptian population and this specific type of lncRNAs may be included in the lists of both potential prognostic biomarkers and the future therapeutic targets for glioblastomas

MicroRNA-34a: A Key Regulator in the Hallmarks of Renal Cell Carcinoma

Renal cell carcinoma (RCC) incidence has increased over the past two decades. Recent studies reported microRNAs as promising biomarkers for early cancer detection, accurate prognosis, and molecular targets for future treatment. This study aimed to evaluate the expression levels of miR-34a and 11 of its bioinformatically selected target genes and proteins to test their potential dysregulation in RCC. Quantitative real-time PCR for miR-34a and its targets; MET oncogene; gene-regulating apoptosis (TP53INP2 and DFFA); cell proliferation (E2F3); and cell differentiation (SOX2 and TGFB3) as well as immunohistochemical assay for VEGFA, TP53, Bcl2, TGFB1, and Ki67 protein expression have been performed in 85 FFPE RCC tumor specimens. Clinicopathological parameter correlation and in silico network analysis have also implicated. We found RCC tissues displayed significantly higher miR-34a expression level than their corresponding noncancerous tissues, particularly in chromophobic subtype. MET and E2F3 were significantly upregulated, while TP53INP2 and SOX2 were downregulated. ROC analysis showed high diagnostic performance of miR-34a (AUC = 0.854), MET (AUC = 0.765), and E2F3 (AUC = 0.761). The advanced pathological grade was associated with strong TGFB1, VEGFA, and Ki67 protein expression and absent Tp53 staining. These findings indicate miR-34a along with its putative target genes could play a role in RCC tumorigenesis and progression

Longevity-Related Gene Transcriptomic Signature in Glioblastoma Multiforme

Glioblastoma multiforme (GBM) (grade IV astrocytoma) has been assumed to be the most fatal type of glioma with low survival and high recurrence rates, even after prompt surgical removal and aggressive courses of treatment. Transcriptional reprogramming to stem cell-like state could explain some of the deregulated molecular signatures in GBM disease. The present study aimed to quantify the expression profiling of longevity-related transcriptional factors SOX2, OCT3/4, and NANOG to evaluate their diagnostic and performance values in high-grade gliomas. Forty-four specimens were obtained from glioblastoma patients (10 females and 34 males). Quantitative real-time polymerase chain reaction was applied for relative gene expression quantification. In silico network analysis was executed. NANOG and OCT3/4 mRNA expression levels were significantly downregulated while that of SOX2 was upregulated in cancer compared to noncancer tissues. Receiver operating characteristic curve analysis showed high diagnostic performance of NANOG and OCT3/4 than SOX2. However, the aberrant expressions of the genes studied were not associated with the prognostic variables in the current population. In conclusion, the current study highlighted the aberrant expression of certain longevity-associated transcription factors in glioblastoma multiforme which may direct the attention towards new strategies in the treatment of such lethal disease

Data supporting the structural and functional characterization of Thrombin‐Activatable Fibrinolysis Inhibitor in breast cancer

The data in this paper is related to the research article entitled “Thrombin-activatable fibrinolysis inhibitor Thr325Ile polymorphism and plasma level in breast cancer: A pilot study” (Fawzy et al., 2015) [1]. Many emerging studies have begun to unravel the pathophysiologic role of the fibrinolytic system in breast cancer (BC) progression (Zorio et al., 2008) [2]. Activation of the fibrinolytic plasminogen/plasmin system results in degradation of protein barriers, thereby mediating cell migration essential for tumor growth, angiogenesis, and dissemination (Castellino and Ploplis, 2005) [3]. In the current study, in silico data analysis of Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) gene and protein has been done. Data have been retrieved from several databases mentioned in details in the text. Determination and analysis of the structural and functional impact of TAFI and its expression could help elucidate the contribution of the TAFI pathway to acquired hemostatic dysfunction and will form the basis of potential therapeutic strategies to manipulate this pathway. An inhibition of TAFI (e.g. by FXI inhibitors) will offer the therapeutic possibilities to improve the decreased fibrinolysis and increase the efficiency of fibrinolytic therapy in thrombotic disorders including cancer

Serum S100B: A possible biomarker for severity of obstructive sleep apnea

Introduction: Obstructive sleep apnea (OSA) is characterized by upper airway collapsibility and intermittent hypoxia (IH) during sleep. It has neurological complications and it has been associated with morbidity and mortality. Increased serum levels of S100B protein indicates brain injury. Early detection of possible complications of OSA patients could improve management of the disease. Study objective: Measurement of serum S100B protein in OSA patients with correlation to the severity of the disease. Patients and methods: Fifty five OSA patients (24 females; 43.6% and 31 males; 56.4%) and 34 control individuals (17 females; 50% and 17 males; 50%) had a sleep apnea monitoring using the SAM equipment, Inter care technologies, model 100, USA, and S100B serum levels were measured after the sleep study at 6.30–7.30 am. Results: S100B serum levels were higher in patients than controls (P < 0.001) and the levels correlated with the apnea/hypopnea index (AHI) (P < 0.001), lowest oxygen saturation (LOS) (P < 0.001), and oxygen desaturation index (ODI) (P < 0.001). Conclusion: Serum S100B protein was significantly elevated in OSA patients and its serum levels correlated with the severity of the disease. Increased serum S100B could indicat brain injury and could be a potential serum biomarker for detection of early neurological complications in OSA patients that could improve the management and care of these patients

Mobile phones electromagnetic radiation and NAD+-dependent isocitrate dehydrogenase as a mitochondrial marker in asthenozoospermia

AbstractNAD+-dependent Isocitrate Dehydrogenase (NAD+-IDH) could be one of the cell phone radiation targets. Enzyme activity alteration may lead to decline in sperm motility during radio-frequency electromagnetic waves (RF-EMW) exposure. The current case control study aimed to investigate the possible relationship between mitochondrial NAD+-IDH activity in human seminal plasma and sperm motility among asthenozoospermic cellular phone users. A total number of ninety idiopathic infertile males referred from the Department of Dermatology and Andrology, were enrolled in this study. NAD+-IDH activity was measured in human seminal plasma by spectrophotometer. Computer-aided sperm analysis (CASA) following WHO criteria has been used for semen analyses. The results showed that IDH activity was increased in patients with prolonged cell phone daily use ≥4 h/day. Its level, correlated negatively with either the motility ratio percentages (r = −0.46, p < 0.001) or the progressive motility percentages (r = −0.50, p < 0.001) in the study groups. The current study suggests that NAD+-IDH in human seminal plasma could be one of seminal plasma biomarkers reflecting the mitochondrial function of spermatozoa. Alteration of its level could reflect the defective motility of sperms among some cases of cellular phone users

IL-37 gene variant (rs3811047): A marker of disease activity in rheumatoid arthritis: A pilot study

Background: Rheumatoid arthritis (RA) is a joint destructive disorder with great morbidity. Unraveling genetic determinants causing the disease would pave the road towards early detection and precise medicine. Interleukin 37 (IL-37), a natural inhibitor of innate immunity, was shown to be a key modulator in RA. Plasma levels were deregulated and correlated with disease activity. Therefore, we hypothesized the IL-37 gene variants could influence the clinical characteristics of RA patients. Objective: This is a pilot study to assess the association of rs3811047 variant of IL-37 gene with RA development and disease activity in an Egyptian population. Methods: A total of 100 individuals (50 RA patients and 50 healthy individuals) were enrolled in the study. Disease activity score of 28 joints (DAS28) was estimated for RA patients. Genotyping was performed using Real-Time PCR technology. Results: There was no statistically significant association between genotype frequencies of rs3811047 and RA risk. However, there was a significant relationship between the studied single nucleotide polymorphism (SNP) and disease activity. Patients carrying the GG genotype had higher DAS28 score than patients with AA or AG genotypes (p = .041). Conclusion: IL-37 gene rs3811047 SNP was associated with more severe RA disease activity in the current population. Larger epidemiological study is warranted to validate our results

Circulating ESR1, long non-coding RNA HOTAIR and microRNA-130a gene expression as biomarkers for breast cancer stage and metastasis

Abstract Breast cancer, the most prevalent cancer among women, has posed a significant challenge in identifying biomarkers for early diagnosis and prognosis. This study aimed to elucidate the gene expression profile of Estrogen Receptor-1 (ESR-1), long non-coding RNA HOTAIR, and microRNA-130a in the serum of Egyptian breast cancer patients, evaluating the potential of HOTAIR and miR-130a as biomarkers for predicting pathological parameters in BC. The study involved 45 patients with primary BC, with serum samples collected preoperatively and postoperatively twice. The expression levels of ESR-1, HOTAIR, and miR-130a were quantified using real-time PCR and analyzed for correlations with each other and with the clinical and pathological parameters of the patients. Serum HOTAIR levels exhibited a strong positive association with metastasis and demonstrated a significant increase after 6 months in all patients with locally advanced and stage IV BC. Conversely, tumors with advanced stages and metastatic lesions showed significantly lower expression levels of miR-130a. Notably, a significant positive correlation was observed between preoperative ESR-1 expression and both HOTAIR and miR-130a levels. Serum HOTAIR and miR-130a levels have emerged as promising non-invasive biomarkers with the potential to predict the pathological features of BC patients. HOTAIR, an oncogenic long non-coding RNA (lncRNA), and miR-130a, a tumor suppressor miRNA, play crucial roles in tumor progression. Further investigations are warranted to elucidate the intricate interplay between HOTAIR and miR-130a and to fully comprehend the contribution of HOTAIR to BC recurrence and its potential utility in early relapse prediction

Association of microRNA-34a rs2666433 (A/G) Variant with Systemic Lupus Erythematosus in Female Patients: A Case-Control Study

Several microRNAs (miRNAs) are associated with autoimmune disease susceptibility and phenotype, including systemic lupus erythematosus (SLE). We aimed to explore for the first time the role of the miRNA-34a gene (MIR34A) rs2666433A &gt; G variant in SLE risk and severity. A total of 163 adult patients with SLE and matched controls were recruited. Real-Time allelic discrimination PCR was applied for genotyping. Correlation with disease activity and clinic-laboratory data was done. The rs2666433 variant conferred protection against SLE development under heterozygous [A/G vs. G/G; OR = 0.57, 95%CI = 0.34–0.95], homozygous [A/A vs. G/G; OR = 0.52, 95%CI = 0.29–0.94], dominant [A/G + A/A vs. GG; OR = 0.55, 95%CI = 0.35–0.88], and log-additive [OR = 0.71, 95%CI = 0.53–0.95] models. Data stratification by sex revealed a significant association with SLE development in female participants under heterozygous/homozygous models (p-interaction = 0.004). There was no clear demarcation between SLE patients carrying different genotypes regarding the disease activity index or patients stratified according to lupus nephritis. Enrichment analysis confirmed the implication of MIR34A in the SLE pathway by targeting several genes related to SLE etiopathology. In conclusion, although the MIR34A rs2666433 variant conferred protection against developing SLE disease in the study population, it showed no association with disease activity. Replication studies in other populations are warranted