Impact of Dysregulated LINC01559 and LINC01410 Expression on the Diagnosis and Survival of Non-Small Cell Lung Cancer.

Lung cancer is a widely recognized cancer with a very low survival rate, as it is mostly diagnosed at advanced stages. The most prevalent type of lung cancer is non-small cell lung cancer (NSCLC). LncRNAs are widely involved in cancer progression and migration. Therefore, we intended to estimate the circulatory expression levels of LINC01559 and LINC01410 in NSCLC and their roles in tumor prognosis evaluation as less invasive potential markers. The relative expression levels of the plasma cell-free lncRNAs LINC01559 and LINC01410 in seventy patients with NSCLC and seventy healthy subjects as controls were measured by real-time PCR. Enzyme-linked immunosorbent assays were utilized to measure carcinoembryonic antigen (CEA) concentrations. The LINC01559 and LINC01410 expression levels were significantly increased in NSCLC patients versus controls. Both lncRNAs showed good performance in the ROC curve analysis with high sensitivity and specificity for distinguishing patients from controls. LINC01559 had the highest AUC in the ROC curve analysis (0.96, 95 CI% CI: 0.93-0.99) for distinguishing patients from controls, while LINC01410 had the highest AUC (0.77, 95 CI% CI: 0.65-0.89) for differentiating metastatic tumors from nonmetastatic tumors. High expression levels of LINC01410 and LINC01559 were associated with low overall survival (log rank = 47.04 and 28.18, respectively, P < 0.001) and low progression-free survival (log rank = 40.68 and 28.77, respectively (P < 0.001)) and with the presence of metastasis. We suggest that LINC01559 and LINC01410 can be used as valuable, high-performing biomarkers in NSCLC diagnosis and prognosis prediction.

Evaluation of the expression levels of lncRNAs H19 and MEG3 in patients with type 2 diabetes mellitus.

BACKGROUND: LncRNAs may play a role in either suppressing or exacerbating diabetes-associated vascular complications. AIMS: This study aimed to assess MEG3 and H19 expression levels in T2DM and pre-diabetes and their roles in diabetes-related microvascular complications. SUBJECT AND METHODS: (RT-PCR) analysis of the MEG3 and H19 plasma levels was carried out in 180 participants of T2DM, pre-diabetes, and control. RESULTS: The expression level of lncRNA H19 was significantly down-regulated and lncRNA MEG3 up-regulated in T2DM compared to pre-diabetes and control, also for pre-diabetes versus control. The (ROC) analysis of MEG3 and H19 relative expression levels showed that MEG3 has better sensitivity for distinguishing T2DM from pre-diabetes and control groups.In comparison, H19 offered superior sensitivity to distinguish pre-diabetic from controls. Additionally, H19 was reported as an independent risk factor for T2DM by multivariate analysis. Low expression of H19 and over-expressed MEG3 were significantly associated with retinopathy, nephropathy, and elevated renal indicators (urea, creatinine, and UACR. CONCLUSION: Our results implicated the potential diagnostic and predictive roles of lncRNA MEG3 and H19 for T2DM and related microvascular complications. Additionally, H19 may serve as a potential biomarker for pre-diabetes prediction.

Long Non-Coding RNAs ASB16-AS1 and AFAP1-AS1: Diagnostic, Prognostic Impact and Survival Analysis in Colorectal Cancer.

Background: We aimed to evaluate the diagnostic roles of AFAP1-AS1 and ASB16-AS1 in colorectal cancer and highlight their roles in predicting colorectal cancer patients' prognosis. Methods: In this case-control study, 146 participants were involved. Group I included 47 patients with CRC. Group II composed of 49 patients with benign lesions in the colon, and Group III included 50 apparently normal subjects of coincided age and gender as controls. All participants were subjected to clinical and endoscopic evaluations, CA19-9, CEA, and quantification of relative expression of lncRNAs ASB16-AS1 and AFAP1-AS1. Results: CRC patients had significantly elevated expression levels of both lncRNAs in tissue and plasma samples versus benign and control groups (p < 0.001). Despite the higher sensitivity of tissue samples results, the relative expression of both lncRNAs in plasma samples was very encouraging in the discrimination between patients with CRC versus control and benign groups. Furthermore, both lncRNAs could discriminate patients with early-stage CRC (stage I&II) from being colonic lesion and control groups with better sensitivity and specificity presented by ASB16-AS1 in tissue and plasma than results detailed by AFAP1-AS1. High expression levels of ASB16-AS1 in tissue and plasma and tissue lncRNA AFAP1-AS1 are significantly correlated with decreased overall survival (p < 0.001) and reduced progression-free (p < 0.001) compared to low expression in CRC patients. Conclusion: We propose the utilization of lncRNA ASB16-AS1 and lncRNA AFAP1-AS1 as biomarkers in diagnosis and prognosis estimation for CRC patients. Moreover, their value in early CRC patients may affect the assortment of target therapy and treatment protocols.

Evaluation of mRNA expression level of the ATP synthase membrane subunit c locus 1 (ATP5G1) gene in patients with schizophrenia.

BACKGROUND: Schizophrenia is a serious, complex mental disorder. The impairment of oxidative phosphorylation has a detrimental consequence on CNS function. Different ATP synthase subunits have been involved in the pathological process of various neurodegenerative disorders. Our goal was to evaluate the mRNA expression level of the ATP synthase membrane subunit c locus 1 (ATP5G1, also named ATP5MC1) gene in patients with schizophrenia. METHODS: Determination of the expression levels of ATP5G1 in plasma and peripheral blood mononuclear cells (PBMCs) were performed by real-time PCR in 90 controls and 90 patients with schizophrenia. RESULTS: Patients had significantly decreased ATP5G1 mRNA expression levels in both plasma and PBMCs compared to controls. The receiver operating characteristic curve was applied to detect a cut-off value of ATP5G1 expression in plasma and PBMCs. The ATP5G1 relative expression in PBMCs had better performance with a cut-off value ≤ 21 (AUC = 0.892, P < 0.001), sensitivity of 94.44%, and specificity of 72.22% in discriminating between schizophrenic patients. ATP5G1 expression in PBMCs was an independent predictor in schizophrenia. CONCLUSION: This study revealed a down-regulation of ATP5G1 expression in schizophrenia, precisely expression in PBMCs. That might give insight into the role of ATP5G1 gene in the pathogenesis of schizophrenia.

Potential impact of serpin peptidase inhibitor clade (A) member 4 SERPINA4 (rs2093266) and SERPINA5 (rs1955656) genetic variants on COVID-19 induced acute kidney injury.

Background: SARS-CoV-2 has a number of targets, including the kidneys. Acute Kidney Injury (AKI) might develop in up to a quarter of SARS-CoV-2 patients. In the clinical environment, AKI is linked to a high rate of death and leads to the progression of AKI to chronic renal disease. Aim: We aimed to investigate rs2093266 and rs1955656 polymorphisms in SERPINA4 and SERPINA5 genes, respectively, as risk factors for COVID-19 induced AKI. Subjects and methods: A case-control study included 227 participants who were divided into three groups: 81 healthy volunteers who served as controls, 76 COVID-19 patients without AKI and 70 COVID -19 patients with AKI. The TaqMan assay was used for genotyping the SERPINA4 (rs2093266) and SERPINA5 (rs1955656) polymorphisms by real-time PCR technique. Results: Lymphocytes and eGFR showed a significantly decreasing trend across the three studied groups, while CRP, d-Dimer, ferritin, creatinine, KIM-1and NGAL showed a significantly increasing trend across the three studied groups (P < 0.001). Rs2093266 (AG and AA) genotypes were significant risk factors among non-AKI and AKI groups in comparison to controls. Rs1955656 (AG and AA) were significant risk factors among the AKI group, while AA was the only significant risk factor among the non-AKI group. Recessive, dominant, co-dominant, and over-dominant models for genotype combinations were demonstrated. The GG v AA, GG + AG v AA, and GG v AG + AA models of the rs2093266 were all significant predictors of AKI, whilst only the GG v AA model of the rs1955656 SNP was a significant predictor. The logistic regression model was statistically significant, χ2 = 56.48, p < 0.001. AKI was associated with progressed age (OR = 0.95, 95% CI: 0.91-0.98, p = 0.006), suffering from chronic diseases (OR = 3.25, 95% CI: 1.31-8.01, p = 0.010), increased BMI (OR = 0.89, 95% CI: 0.81-0.98, p = 0.018), immunosuppressive (OR = 4.61, 95% CI: 1.24-17.16, p = 0.022) and rs2093266 (AG + AA) (OR = 3.0, 95% CI: 1.11-8.10, p = 0.030). Conclusion: Single nucleotide polymorphisms (rs2093266) at SERPINA4 gene and (rs1955656) at SERPINA5 gene were strongly linked to the development of AKI in COVID-19 patients.

Inverse relationship between the level of miRNA 148a-3p and both TGF-ß1 and FIB-4 in hepatocellular carcinoma.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a major health burden globally. Dysregulation of miRNA 148a-3p is engaged in carcinogenesis. TGF-ß is a profibrogenic cytokine. This study assesses the expression level of miRNA 148a-3p and its relationship with serum TGF-ß1 and fibrosis index based on four factors (FIB-4) in Egyptian patients with HCV-associated HCC. SUBJECTS: and Methods: The study included 72 HCC patients with HCV, 48 HCV cirrhotic patients, and 47 healthy controls. Serum TGF-ß1 was assessed by ELISA and the expression of miRNA 148a-3p was measured by RT-PCR. RESULTS: Patients with HCC had lower plasma miRNA 148a-3p, higher serum TGF-ß1, and higher FIB-4 levels than patients with cirrhosis and controls. miRNA 148a-3p discriminated HCC either from control (AUC: 0.997, 95.83% sensitivity, 85.11% specificity) or from cirrhosis (AUC: 0.943, 91.67% sensitivity, 81.25% specificity). Moreover, it distinguished metastatic from nonmetastatic patients (AUC: 0.800, 88.89% sensitivity, 60.0% specificity). The decreased miRNA 148a-3p and the increased TGF-ß1 levels were related to distant metastasis, multinodular lesions, advanced TNM stage, and BCLC score (C). A negative correlation between miRNA 148a-3p and each of FIB-4 and TGF-ß1 was detected. The decreased miRNA 148a-3p was associated with poor overall survival and poor progression-free survival. CONCLUSION: An inverse relationship between miRNA 148a-3p and both TGF-ß1 and FIB-4 was observed, which could be involved in HCC pathogenesis. Moreover, this miRNA is a potential diagnostic and prognostic biomarker for HCC.

Role of Adiponectin Gene and Receptor Polymorphisms and Their mRNA Levels with Serum Adiponectin Level in Myocardial Infarction.

BACKGROUND AND AIM: Genetic factors are vital participants in the development and progression of myocardial infarction (MI). Adiponectin has been assumed to have a protective role in MI and adiponectin receptors variants could be a determinant for atherosclerosis. We aimed to evaluate the prevalence of ADIPOQ (rs2241766) and ADIPOR2 (rs10773989) polymorphisms and their association with mRNA levels and circulatory adiponectin levels in patients with MI. SUBJECTS AND METHODS: A total of 220 participants were classified into two groups: group 1 included 120 patients with MI, and group 2 involved 100 healthy participants as controls. Genotyping of ADIPOQ (rs2241766) and ADIPOR2 (rs10773989) polymorphisms were analyzed using an allele discrimination assay with real-time PCR and their relative expression or mRNA levels were determined by real-time PCR. Serum adiponectin level was determined using an ELISA technique. RESULTS: The ADIPOQ rs2241766 GG genotype and G allele and the CC genotype and C allele of ADIPOR2 rs10773989 were significantly prevalent in patients with MI and associated with increased risk of MI. We detected a marked reduction in serum adiponectin, ADIPOQ and ADIPOR2 mRNA levels in patients than control. The GG genotype of ADIPOQ rs2241766 and the CC genotype of ADIPOR2 rs10773989 had the lowest levels of their mRNA and adiponectin level in both patients and controls. CONCLUSION: Adiponectin gene and receptor variants are potentially related to MI risk; furthermore, their expressions were markedly depressed in MI which suggests their use as potential biomarkers for MI.

Cell-free long non-coding RNAs (LY86-AS1 & HCG27_201and GAS5) as biomarkers for pre-diabetes and type 2 DM in Egypt.

BACKGROUND: Increasing interest has been focused on lncRNAs as potential markers in the pathogenesis and progression of numerous diseases. AIM: We aimed to investigate the expression pattern and role of cell-free lncRNAs (GAS5, HCG27_201 and LY86-AS1) in pre-diabetic, diabetic and T2DM groups. SUBJECTS & METHODS: Quantification of the expression level of cell-free lncRNAs (GAS5, HCG27_201 and LY86-AS1) was performed by real-time PCR in 210 individuals classified in diabetic (T2DM), pre-diabetic and control groups. RESULTS: Significant differences were observed in the relative expression level of lncRNAs (GAS5, LY86-AS1 and HCG27_201) among the three studied groups. The LncRNA expression levels decreased gradually from the control to the pre-diabetic group and reached the lowest values in the T2DM group. The A receiver operating characteristic curve (ROC) was applied to identify a cut-off value for each of the three genes among our groups. The three lncRNAs showed promising results in discriminating between the diabetic patients and controls, with HCG27_201 gene expression having the best performance. Furthermore, lncRNA expression was able to predict the future development of DM in the pre-diabetics because ROC analysis among diabetics and pre-diabetics revealed considerable results. GAS5 gene expression showed the best performance. Additionally, HCG27_201 expression was the most valuable biomarker for differentiating between pre-diabetics and controls and presented a sensitivity of 91% and specificity of 64%. CONCLUSIONS: We concluded that cell free lncRNAs (GAS5, LY86-AS1 and HCG27_201) could be considered promising diagnostic and predictive biomarkers for DM and that HCG27_201 could act as a potential diagnostic biomarker for pre-diabetes.

Evaluation of ASPM and TEF Gene Expressions as Potential Biomarkers for Bladder Cancer.

Bladder cancer is one of the most predominant tumors of the genitourinary tract. In addition to pathological findings, the molecular modifications that might affect tumorigenesis and tumor outcome should be considered when treating bladder cancer. Accordingly, we aimed to investigate the expression levels of both the ASPM and TEF genes in bladder cancer tissues and their value in disease prognosis. The expression levels of the ASPM and TEF genes were analyzed by quantitative real-time PCR (qRT-PCR) in 90 bladder cancer tissue specimens and 90 specimens of normal urinary bladder tissue taken away from the tumor site. The upregulation of ASPM expression and the downregulation of TEF expression were observed in bladder cancer tissues compared to adjacent normal tissues, and these levels were correlated with high-grade tumors, advanced stage disease and the presence of metastasis. Both genes had the ability to predict metastatic association with sensitivity (84.62%) and specificity (68.42%; *P < 0.001) for the ASPM gene and for the TEF gene with sensitivity (80.77%) and specificity (78.95%; *P < 0.001). Additionally, Kaplan-Meier survival analysis indicated that elevated ASPM expression levels and reduced TEF expression levels significantly correlated with decreased overall survival and progression-free survival. The current analysis concludes that ASPM and TEF expressions might be used as potential biomarkers in bladder cancer patients.

Simultaneous Assessment of MicroRNAs 126 and 192 in Diabetic Nephropathy Patients and the Relation of these MicroRNAs with Urinary Albumin.

BACKGROUND AND OBJECTIVE: Diabetic nephropathy (DN) is a major determinant of end-stage renal disease (ESRD). Altered microRNA levels lead to serious chronic diseases, such as diabetes. We aimed to measure the expression levels of two microRNAs, microRNA126 and 192 in DN and investigate their connection with albuminuria levels. METHODS: This study included 229 subjects (134 DN patients and 95 controls). Serum lipid profiles, glucose levels, glycated haemoglobin (HbA1c) levels, and renal functions were assayed. The microRNA126 and microRNA192 expression levels were determined by real-time PCR. RESULTS: Patients with DN had higher weights, BMI values, glucose levels (P<0.001), HbA1c levels (P<0.001), urinary albumin-creatinine ratio (ACR) values (P<0.001), urea levels (P=0.002), and creatinine levels (P=0.004) and lower expression levels of both microRNA192 (P<0.001) and microRNA126 (P<0.001) than controls. MicroRNA126 expression was positively correlated with age, estimated glomerular filtration rate (eGFR) and microRNA192 expression but negatively correlated with blood sugar, HbA1c, urea, creatinine and ACR. MicroRNA192 had higher sensitivity (91%), specificity (94%), and area under the curve (AUC) (0.967) values than microRNA126 (sensitivity, 90%; specificity, 68%; AUC, 0.897) and thus can precisely diagnose DN. CONCLUSION: Both MicroRNA126 and microRNA192 expression were obviously associated with DN and might determine the progression of the disease owing to prominent relation with macroalbuminuria.

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.