Association between genetic variants of GRM7 (rs1396409 and rs9883258) and treatment outcomes in Schizophrenic Egyptian patients.

BACKGROUND AND AIM: This study evaluated the association between rs1396409 and rs9883258 and the risk of schizophrenia (SCZ) and treatment outcomes in Egyptian patients. METHODS: This study included 88 patients with SCZ and 88 healthy controls. Lipid profile was assayed. Genotyping of rs1396409 and rs9883258 polymorphisms was analyzed using real-time PCR. RESULTS: The rs1396409 AG genotype frequency was significantly associated with SCZ risk (p = 0.002). Also, significant increased risk of SCZ was observed under allelic (p = 0.001), dominant (p = 0.001) and overdominant (p = 0.001) genetic model of rs1396409. However, rs9883258 AA genotype revealed nonsignificant association with SCZ. Cases with the rs1396409AG genotype exhibited hypertriglyceridemia (p < 0.001) and hypercholesterolemia (p = 0.001). In total, 72.3% and 74.5% of the cases presented with rs1396409 AG have negative symptoms (p = 0.022) and exhibited poor drug response (p = 0.023), respectively; all cases with rs1396409 GG genotype attempted suicide (p = 0.002) and are drug-free (p = 0.003). SCZ patients with negative symptoms had hypercholesterolemia (p = 0.008) mainly low-density lipoproteins (LDLc) (p = 0.016), and those with cognitive symptoms presented with low level of high-density lipoprotein (HDLc) (p = 0.023). Moreover, the multivariate regression analysis revealed that both rs1396409 G allele and HDLc were predictors of SCZ (p = 0.003 and 0.001, resp.). CONCLUSION: The current study concluded that metabotropic glutamate receptor 7 (GRM7) rs1396409 AG could be a potential biomarker for SCZ diagnosis. It also revealed an independent association between the GRM7 rs1396409 G allele, HDLc and SCZ development.

Various Expressions of PIK3C2A and TXNIP Genes and Their Potential Role as Independent Risk Factors for Chronic Stable Angina and Acute Coronary Syndrome.

BACKGROUND AND AIM: Genetic factors play a significant role in the onset and progression of coronary artery disease (CAD). PIK3C2A may contribute to the development of acute coronary syndrome (ACS) by affecting blood glucose levels and oxidative stress. The expression levels of TXNIP were significantly higher in patients with unstable angina pectoris. However, the situation is different in ACS. In the current study, we aim to investigate the role of PIK3C2A and TXNIP as independent risk factors for chronic stable angina (CSA) and ACS. SUBJECTS AND METHODS: This study involved 215 subjects (60 patients with CSA, 55 patients with ACS, and 100 controls). All subjects were exposed for assaying gene expressions of PIK3C2A and TXNIP by quantitative real-time polymerase chain reaction. RESULTS: It was found that TXNIP was upregulated, whereas PIK3C2A was downregulated in patients with CAD compared to the control group. PIK3C2A was significantly downregulated in patients with ACS compared to that in patients with CSA (p < 0.001), but TXNIP was not (p = 0.7). TXNIP was significantly upregulated in STEMI-ACS patients compared to CSA (p = 0.045) and NSTEMI ACS (p = 0.046), among non-diabetic (p = 0.023) smokers (p = 0.036) with hypertension (p = 0.005) and hypercholesterolemia (p = 0.001). ROC (receiver operating characteristic) curve analysis revealed that PIK3C2A (0.981; p < 0.001; 98.18) was the most sensitive mRNA for discriminating ACS from control, followed by TXNIP (0.775; p < 0.001; 70.91). However, for discriminating ACS from CSA combined mRNAs, (PIK3C2A + TXNIP) (0.893; p < 0.001; 98.18) and PIK3C2A (0.892; p < 0.001; 81.82) are promising biomarkers. On the other hand, the most sensitive mRNA for differentiating CSA from control is mRNAs (PIK3C2A + TXNIP) (0.963; p < 0.001; 95), then TXINP (81.3; p < 0.001; 93.33), and finally, PIK3C2A (0.782; p < 0.001; 81.67). In the multivariate regression model, PIK3C2A ((p = 0.002), 0.118 (0.031-0.445)) and smoking status ((p = 0.034); 0.151 (0.026-0.866)) were independent variables for ACS. Moreover, PIK3C2A ((p < 0.013); 0.706 (0.614-0.812)), Hb ((p = 0.013); 0.525 (0.317-0.871)), and total cholesterol ((p = 0.04); 0.865 (0.784-0.955)) were significantly (p < 0.05) and independently related to the prognosis of CSA. Furthermore, PIK3C2A ((p = 0.002), 0.923 (0.877-0.971)), TXNIP ((p = 0.001); 2.809 (1.558-5.064)) the body weight ((p = 0.033); 1.254 (1.018-1.544)) were independently associated with CSA. CONCLUSIONS: Our study concluded that the dysregulated mRNA PIK3C2A and TXNIP gene expressions may be useful in diagnosis of CAD and prediction of ACS development.

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.

Deregulation of CircANXA2, Circ0075001, and CircFBXW7 Gene Expressions and Their Predictive Value in Egyptian Acute Myeloid Leukemia Patients.

Background: Acute myeloid leukemia (AML) is of heterogeneous pathogenesis and caused by alterations of multiple genes. CircRNAs act as oncogenes or tumor suppressors in numerous tumors and could be novel diagnostic and prognostic biomarkers. Few studies had incorporated circRNAs in AML. Aim of the Work: Assessment of circANXA2, circ0075001, and circFBXW7 gene expressions in AML patients. Evaluation of their relations with clinical, cytogenetic, and overall survival outcome to emphasize their diagnostic role and prognostic impact. Methods: This study was carried out on 120 subjects (66 AML patients and 54 controls). All subjects were subjected to gene expressions assay for circANXA2, circ0075001, circFBXW7 by quantitative real-time polymerase chain reaction. Results: Prominent overexpression of circANAX2 and circ0075001 in patients than control (P < 0.001), whereas circFBXW7 was markedly downregulated in patients than in control (P < 0.001). Moreover, circANXA2 with AUC 0.824, P <0.001, had a sensitivity of 74.24%, specificity 88.89% whereas circ0075001 with AUC 0.855, P < 0.001, had the highest sensitivity of 83.33% and specificity 79.63%, and circFBXW7 with AUC 0.826, P < 0.001, had a sensitivity of 75.76% and specificity 74.07% in the distinction of AML patients from controls. Additionally, we find out that high expression of circANXA2 and circ0075001 correlated significantly with splenomegaly, hepatomegaly, less differentiated FAB subtypes (M5, M7), short overall survival, and had an adverse cytogenetic pattern. Conclusion: CircANXA2, circ0075001, and circFBXW7 gene expressions could serve as potential diagnostic biomarkers for AML disease. Moreover, CircANXA2 and circ0075001 exert poor prognostic effects on AML patients.

On-admission plasma levels of BNP, MR-proADM, and cTnI in pediatric heart failure: contributions to diagnosis, prognosis, and outcome.

BACKGROUND: The aim of this study is to evaluate the use of on-admission plasma levels of BNP, MR-proADM, and cTnI in diagnosing the clinical severity and progression of heart failure (HF) in children with CHD. Also, to correlate the levels of these biomarkers with the HF outcome (survival versus in-hospital mortality). RESULTS: A prospective cohort study conducted in period from January 2017 to March 2018. All children presenting with HF had a Ross score assessment, echocardiography, and on-admission plasma level assay of BNP, MR-proADM, and cTnI. Patients were followed clinically throughout their hospital stay. The discriminatory power of on-admission measurement of each biomarker was determined using the receiver-operating characteristic (ROC). The results showed a significantly high on-admission plasma level of the 3 biomarkers among CHD cohort children than healthy controls (p < 0.001). Linear correlation was noted between the 3 biomarkers with Ross score, ejection fraction, and duration of hospital stay. Furthermore, significant association between on-admission level of the 3 biomarkers (BNP, MR-proADM, and cTnI) with patient's in-hospital mortality (p = 0.0003, Beta coefficient = 0.842; p = 0.0495, Beta coefficient = 0.183; and p < 0.001, Beta coefficient = 0.635, respectively), with on-admission BNP (cut of point 507.13) predicting in-hospital mortality, with 95.5% sensitivity, 88% specificity. CONCLUSIONS: There is a high diagnostic value of measuring the on-admission levels of BNP, MR-proADM, and cTnI regarding the clinical severity and disease progression in the setting of pediatric heart failure, but the BNP level was more superior in prediction of the patients' outcome.

Relation of Procollagen Type III Amino Terminal Propeptide Level to Sepsis Severity in Pediatrics.

BACKGROUND: Sepsis is still the main etiology of mortality in pediatric intensive care units (PICUs). Therefore, we performed this study to evaluate the value of procollagen Type III amino-terminal propeptide (PIIINP) as a biomarker for sepsis severity diagnosis and mortality. METHOD: A prospective study was carried out on 170 critically ill children admitted into the PICU and 100 controls. The performed clinical examinations included calculation of the pediatric risk of mortality. Serum PIIINP was withdrawn from patients at admission and from the controls. RESULTS: PIIINP level was significantly more increased in sepsis, severe sepsis, and septic shock than among the controls (p < 0.001). PIIINP was significantly higher in severe sepsis and septic shock (568.3 (32.5-1304.7) and 926.2 (460.6-1370), respectively) versus sepsis (149.5 (29.6-272.9)) (p < 0.001). PIIINP was significantly increased in non-survivors (935.4 (104.6-1370)) compared to survivors (586.5 (29.6-1169)) (p < 0.016). ROC curve analysis exhibited an area under the curve (AUC) of 0.833 for PIIINP, which is predictive for sepsis, while the cut-off point of 103.3 ng/mL had a sensitivity of 88% and specificity of 82%. The prognosis of the AUC curve for PIIINP to predict mortality was 0.651; the cut-off of 490.4 ng/mL had a sensitivity of 87.5% and specificity of 51.6%. CONCLUSIONS: PIIINP levels are increased in sepsis, with significantly higher levels in severe sepsis, septic shock, and non-survivors, thus representing a promising biomarker for pediatric sepsis severity and mortality.

Prognostic Impact of Genetic Variants of MECP2 and TIRAP on Clinical Outcomes of Systemic Lupus Erythematosus with and without Nephritis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune illness with a growing prevalence in many populations. Few studies have examined genetic predisposition to SLE, so we aimed to examine the clinical impact of the genetic polymorphisms MECP2 rs2734647and TIRAP rs8177374 on the outcomes and therapeutic precision of SLE with and without nephritis. This study included 110 SLE patients-divided into 63 with lupus nephritis (LN), and 47 without nephritis-and 100 controls. Laboratory measurements including CRP, ESR, ACR, CBC, anti-ds-DNA, vitamin A, C3, and C4 were carried out, along with genotyping of MECP2 rs2734647and TIRAP rs8177374 by real-time PCR and sequencing. Treg %, vitamin A, C3, and C4 were lower, whereas Th17 % was higher, in patients vs. controls (p < 0.001). The T allele of MECP2 rs2734647 was higher in LN than in non-nephritis and control subjects. Moreover, the T allele of TIRAP rs8177374 was higher in LN than in non-nephritis and control subjects. The MECP2 and TIRAP genes could play a role in predisposition to SLE, and can also predict disease progress to nephritis, helping to personalize medicine.

Down regulation of miR-30a-5p and miR-182-5p in gastric cancer: Clinical impact and survival analysis.

BACKGROUND AND AIM: Gastric Cancer (GC) is a leading cause of morbidity and mortality worldwide, particularly in developing nations, only a few suitable gastric cancer serum biomarkers with acceptable sensitivity and specificity exist. This work aims to highlight and uncover miR-30a-5p and miR-182-5p's diagnostic roles regarding gastric cancer and their roles in predicting prognosis. METHODS: 148 patients participated in this study. Groups I, II, and III had 47 patients with GC, 54 patients with benign gastric lesions, and 47 apparently healthy subjects of coincided age and gender as controls, respectively. All participants were clinically evaluated and subjected to CBC, serum CEA, and CA19-9 by ELISA, and real-time PCR tests of miR-30a-5p and miR-182-5p. RESULTS: MiR30a-5p and miR-182-5p were down regulated in gastric cancer patients in Group I more than Groups II and III (P < 0.001). ROC curve analysis revealed that miR30a-5p had better AUC, sensitivity, and specificity (0.961%, 93.62%, and 90.74%respectively). When miR-182-5p was gathered with CEA and CA19-9, specificity raised to 98.15% and PPV to 97.6%. Lower miR-30a-5p levels are linked with the presence of distant metastases, advanced TNM stage, and degree of pathological differentiation of tumors in GC patients (p = 0.034, 0.019, 0.049) respectively. According to the multivariate analysis, miR30a-5p expression level could be an independent predictor of GC. CONCLUSION: Our results exhibited that miRNAs, miR-30a-5p and miR182-5p, gene expression have a diagnostic power and can identify patients with GC. MiR-30a-5p displayed the highest diagnostic specificity and sensitivity. Besides other known tumor markers, they could offer simple noninvasive biomarkers that predict gastric cancer.

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.

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.

Vitamin D deficiency and vitamin D receptor variants in mothers and their neonates are risk factors for neonatal sepsis.

BACKGROUND AND AIM: Increasing prevalence of neonatal sepsis in recent years catch attention to early prevention and management. Vitamin D receptor (VDR) polymorphism can modulate VDR expression level that greatly influences immunity and susceptibility to microbial infections. We aimed to investigate the association of VDR polymorphism at FokI, rs2228570 T/C, and TaqI, rs731236 C/T gene with serum 25-hydroxyvitamin D level and risk of neonatal sepsis. METHODS: This work carried on 160 subjects classified into 80 cases (40 mothers and their 40 septic neonates) and 80 healthy controls (40 volunteer mothers and their 40 healthy neonates). Genotyping of VDR polymorphisms were assayed by real-time PCR and serum 25-hydroxyvitamin D level and hs-CRP were measured by ELISA. RESULTS: Vitamin D deficiency was observed in mothers of cases compared with healthy ones (p = <0.001) and in septic neonates versus healthy ones (p = <0.001). Septic neonates had much higher VDR FokI TT genotype (p = 0.014) and T allele (p = 0.003) versus healthy ones. TT genotype and T allele could increase the risk of sepsis with OR 95% CI [4.804 (1.4-16.4)] and [2.786 (1.4-5.7)] respectively while VDR TaqI showed no association with sepsis. There was a strong LD between FokI and TaqI in sepsis cases. In sepsis, T/T genotype at FokI had significantly lower vitamin D (p = <0.001). CONCLUSION: Vitamin D deficiency in mothers/neonates is a risk factor for neonatal sepsis. VDR FokI T allele had lower 25-hydroxyvitamin D level that may predispose to sepsis hazards.