Predictors and determinants of albuminuria in people with prediabetes and diabetes based on smoking status: A cross-sectional study using the UK Biobank data.

Background: Smoking is attributed to both micro- and macrovascular complications at any stage of metabolic deregulation including prediabetes. Current global diabetes prevention programmes appear to be glucocentric, and do not fully acknowledge the ramifications of cardiorenal risk factors in smokers and ex-smokers. A more holistic approach is needed to prevent vascular complications in people with prediabetes and diabetes before and after quitting. Methods: A cross-sectional study was carried out on participants who agreed to take part in the UK Biobank dataset at the time of their first attendances between March 01, 2006, and December 31, 2010. Those who had their urinary albumin concentration (UAC) data available were included, and those who did not have this data, were excluded. A logistic regression model was fitted to explore the relationship between cardiorenal risk factors and albuminuria in people with prediabetes and diabetes, based on smoking status. Findings: A total of 502,490 participants were included in the UK Biobank dataset. Of them, 30.4% (n=152,896) had their UAC level recorded. Compared with non-smokers, the odds of albuminuria in smokers with prediabetes and diabetes were 1.21 (95% CI 1.05 - 1.39, p=0.009), and 1.26 (95% CI 1.10 - 1.44, p=0.001), respectively. The odds declined after quitting in both groups, but it was not statistically significant (p>0.05). Each unit increase in HbA1c was associated with equivalent increased odds of albuminuria in current and ex-smokers, OR 1.035 (95% CI 1.030 - 1.039, p<0.001), and 1.026 (95% CI 1.023 - 1.028, p <0.001), respectively. Compared to females, male ex-smokers were at 15% increased odds of albuminuria. In ex-smokers, each unit increase in waist circumference was associated with 1% increased risk of albuminuria. Compared with the least deprived quintiles, the odds of albuminuria in the most deprived quintiles, in current and ex-smokers were identical, OR 1.18 (95% CI 1.04-1.324, p=0.010), and 1.19 (95% CI 1.11 - 1.27, p<0.001), respectively. Interpretation: Male smokers are at a higher risk of albuminuria after smoking cessation. Monitoring waist circumference in quitters may identify those who are at a higher risk of albuminuria. Combining smoking cessation intervention in smokers with prediabetes in the current diabetes prevention programmes may offset post-cessation weight gain and reduce the risk of albuminuria. Funding: University of Sheffield.

Long intergenic non-coding RNA, regulator of reprogramming (LINC-ROR) over-expression predicts poor prognosis in renal cell carcinoma.

INTRODUCTION: Long intergenic non-coding RNA, regulator of reprogramming (LINC-ROR) is a newly identified cytoplasmic long non-coding RNA (lncRNA) implicated in cell longevity and apoptosis. We aimed in the current work for the first time to investigate the association of the expression profiles of LINC-ROR and three stem-related transcriptional factors with clinicopathological data and their impact on renal cell carcinoma (RCC) progression in a sample of RCC patients. MATERIAL AND METHODS: Expression levels of LINC-ROR and stemness-related factors: SOX2, NANOG, and POU5F1 were detected in 60 formalin-fixed, paraffin-embedded tissues, and their paired adjacent non-cancer tissues (n = 60) by using real-time qRT-PCR analysis. Additionally, the expression profiles were compared with the available clinicopathological features. RESULTS: The genes studied were markedly up-regulated in RCC (medians and interquartile ranges were 30.3 (1.84-235.5), 10.2 (1.84-53.9), 5.39 (0.94-23.5), and 12.5 (1.61-43.2) for LINC-ROR, SOX2, NANOG, and POU5F1, respectively) relative to paired non-cancer tissue. High expression levels were associated with poor prognosis in terms of tumour undifferentiation (for LINC-ROR, SOX2, and NANOG), lymph node infiltration (for SOX2), postoperative recurrence (for LINC-ROR and SOX2), and shorter overall survival (OS) and progression-free survival (for all genes studied). The best curve for OS prediction was constructed with LINC-ROR data (area under the receiver operating characteristic curve (AUC) = 0.804 at a cut-off value of 72.7, sensitivity 78.9%, and specificity 80.5%). CONCLUSIONS: Collectively, aberrant LINC-ROR and pluripotent gene expression may be recognised as prognostic markers for RCC. Future functional studies are highly recommended to validate the study findings.

Unleash multifunctional role of long noncoding RNAs biomarker panel in breast cancer: a predictor classification model.

Aim: We aimed to explore the circulating expression profile of nine lncRNAs (MALAT1, HOTAIR, PVT1, H19, ROR, GAS5, ANRIL, BANCR, MIAT) in breast cancer (BC) patients relative to normal and risky individuals. Methods: Serum relative expressions of the specified long non-coding RNAs were quantified in 155 consecutive women, using quantitative reverse-transcription PCR. Random Forest (RF) and decision tree were also applied. Results: Significant MALAT1 upregulation and GAS5 downregulation could discriminate risky women from healthy controls. Overexpression of the other genes showed good diagnostic performances. Lower GAS5 levels were associated with metastasis and recurrence. RF model revealed a better performance when combining gene expression patterns with risk factors. Conclusion: The studied panel could be utilized as diagnostic/prognostic biomarkers in BC, providing promising epigenetic-based therapeutic targets.

Association of long non-coding RNA MIAT and MALAT1 expression profiles in peripheral blood of coronary artery disease patients with previous cardiac events.

Long non-coding RNAs (lncRNAs) are implicated in various cellular and pathological processes. Two lncRNAs, myocardial infarction-associated transcript (MIAT) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), may be involved in the pathogenesis of coronary artery disease (CAD). Here, we aimed to determine the relative circulating levels of MIAT and MALAT1 in 110 stable CAD patients and 117 controls and to correlate their levels with the clinical and laboratory data. Peripheral blood expression levels were quantified by Real-Time qPCR. The median MIAT expression level in CAD patients was significantly 12-fold higher than controls (p<0.001). Otherwise, the median MALAT1 expression level was comparable in patient and control groups. Both lncRNAs showed significantly higher relative expression levels in patients with positive history of previous cardiac ischemic events, and MIAT showed significantly higher expression in diabetic CAD patients. The area under the curve of MIAT (0.888 ± 0.02 with sensitivity 95.5% and specificity 72.7%), was significantly larger than that of MALAT1 (0.601 ± 0.04 with sensitivity 50% and specificity 63.6%) for detecting the presence of significant CAD. The current findings suggest that lncRNA MIAT could have a diagnostic significance in CAD patients. MALAT1 levels, however, are not sufficiently reliable to have much clinical use in our cases.

Deregulated MicroRNA Signature Following Glioblastoma Irradiation.

Glioblastoma (GBM), the most common and aggressive brain tumor in adults, shows resistance to treatment, particularly radiotherapy. One method for effective treatment is using a group of radiosensitizers that make tumor cells responsive to radiotherapy. A class of molecules whose expression is affected by radiotherapy is the microRNAs (miRNAs) that present promising regulators of the radioresponse. Eighteen miRNAs (miR-26a, -124, -128, -135b, -145, -153, -181a/b, -203, -21, -210, -212, -221/222, -223, -224, -320, and -590), involved in the pathogenesis of GBM and its radioresponsive state, were reviewed to identify their role in GBM and their potential as radiosensitizing agents. MicroRNAs-26a, -124, -128, -145, -153, -181a/b, -203, -221/222, -223, -224, -320, and -590 promoted GBM radiosensitivity, while microRNAs-135b, -21, -210, and -212 encouraged radioresistance. Ectopic overexpression of the radiosensitivity promoting miRNAs and knockdown of the radioresistant miRNAs represent a prospective radiotherapy enhancement opportunity. This offers a glimmer of hope for a group of the most unfortunate patients known to medicine.

Expression of long intergenic non-coding RNA, regulator of reprogramming, and its prognostic value in patients with glioblastoma.

BACKGROUND: Long intergenic non-coding RNA, regulator of reprogramming ( LINC-ROR) is a newly identified cytoplasmic long non-coding RNA (lncRNA), which has been found to be dysregulated in different cancers. The present work aimed to quantify LINC-ROR expression profile and assess the tumor proteins p53 and caspase 3 expressions in glioblastoma tissue specimens compared to non-cancer tissues, and to correlate these expression levels with the available clinicopathological and survival data. METHODS: LINC-ROR relative expression in 57 glioblastoma cancer tissues and 10 non-cancer tissues was quantified by real-time polymerase chain reaction (qPCR). In addition, methylation-specific PCR of O-6-methylguanine-DNA methyltransferase ( MGMT) promoter and immunohistochemical expression of apoptosis related proteins: p53 and caspase 3 were performed. RESULTS: The up-regulation of LINC-ROR was encountered in 89.5% of patients. The higher expression of LINC-ROR was associated with poor disease progression-free and overall survival as well as a younger age of patients ( P=0.036). p53 protein was expressed only in glioblastoma but not in non-cancer tissues while caspase 3 was weakly expressed in most non-cancer tissues and in varying degrees in glioblastoma (24% weak, 30% moderate, and 16% strong expression). The Kaplan-Meier survival plot illustrated poor survival in glioblastoma patients with over-expressed LINC-ROR ( P=0.010) and down-regulated p53 ( P=0.002). Multivariate analysis showed that glioblastoma patients were clustered into two distinct groups based on LINC-ROR expression profile, p53 staining levels and patients' overall survival. CONCLUSIONS: LINC-ROR up-regulation may have a role in glioblastoma tumorigenesis and could be a potential prognostic marker for this fatal disease.

Comprehensive data analysis for development of custom qRT-PCR miRNA assay for glioblastoma: a prevalidation study.

AIM: Glioblastoma (GB) is one notable example of miRNA-modulated neoplasms. Given its unique expression signature, proper miRNA profiling can help discriminate between GB and other types of brain tumors. The current work aimed to develop a more GB-specific and applicable custom designed quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) miRNA assay. MATERIALS & METHODS: A comprehensive data analysis of bioinformatics databases, previous literature and commercially available pre-designed miRNA PCR arrays within the market. RESULTS: A highly enriched panel of 84 deregulated and GB-specific miRNAs has been developed. CONCLUSION: After validation of this newly developed array, it can not only save the researcher's time and effort, but can also have a potential diagnostic and/or prognostic role in GB, paving the road toward personalized medicine.

Dual biomarkers long non-coding RNA GAS5 and microRNA-34a co-expression signature in common solid tumors.

Accumulating evidence indicates that non-coding RNAs including microRNAs (miRs) and long non-coding RNAs (lncRNAs) are aberrantly expressed in cancer, providing promising biomarkers for diagnosis, prognosis and/or therapeutic targets. We aimed in the current work to quantify the expression profile of miR-34a and one of its bioinformatically selected partner lncRNA growth arrest-specific 5 (GAS5) in a sample of Egyptian cancer patients, including three prevalent types of cancer in our region; renal cell carcinoma (RCC), glioblastoma (GB), and hepatocellular carcinoma (HCC) as well as to correlate these expression profiles with the available clinicopathological data in an attempt to clarify their roles in cancer. Quantitative real-time polymerase chain reaction analysis was applied. Different bioinformatics databases were searched to confirm the potential miRNAs-lncRNA interactions of the selected ncRNAs in cancer pathogenesis. The tumor suppressor lncRNA GAS5 was significantly under-expressed in the three types of cancer [0.08 (0.006-0.38) in RCC, p <0.001; 0.10 (0.003-0.89) in GB, p < 0.001; and 0.12 (0.015-0.74) in HCC, p < 0.001]. However, levels of miR-34a greatly varied according to the tumor type; it displayed an increased expression in RCC [4.05 (1.003-22.69), p <0.001] and a decreased expression in GB [0.35 (0.04-0.95), p <0.001]. Consistent to the computationally predicted miRNA-lncRNA interaction, negative correlations were observed between levels of GAS5 and miR-34a in RCC samples (r = -0.949, p < 0.001), GB (r = -0.518, p < 0.001) and HCC (r = -0.455, p = 0.013). Kaplan-Meier curve analysis revealed that RCC patients with down-regulated miR-34a levels had significantly poor overall survival than their corresponding (p < 0.05). Hierarchical clustering analysis showed RCC patients could be clustered by GAS5 and miR-34a co-expression profile. Our results suggest potential applicability of GAS5 and miR-34a with other conventional markers for various types of cancer. Further functional validation studies are warranted to confirm miR-34a/GAS5 interplay in cancer.