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      Combination of three miRNA (miR-141, miR-21, and miR-375) as potential diagnostic tool for prostate cancer recognition

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          Abstract

          Purpose

          Prostate cancer (PCa) is a common tumor disease in western countries and a leading cause of cancer-driven mortality in men. Current methods for prostate cancer detection, like prostate-specific antigen screening, lead to significant overtreatment. The purpose of the study was to analyze circulating microRNAs in serum as non-invasive biomarkers in patients with diagnosis of prostate cancer and healthy individuals.

          Methods

          This preliminary study included a population of 20 patients with mean age of 68.6 years and mean PSA of 21.3 ng/ml. Eight healthy patients were used as control. MiRNAs were quantified in the total RNA fraction extracted from serum and levels of five microRNAs (miR-106b, miR-141, miR-21, mir-34a, and miR-375) were quantified by RT-qPCR. Statistical analyses evaluated correlation between clinicopathological data and miRNAs expression levels.

          Results

          Relative expression ratios of miR-106b, miR-141-3p, miR-21, and miR-375 were significantly increased (1.8-,  1.9-, 2.4-, and 2.6-fold, respectively) in the PCa group compared to healthy control. Using receiver operating characteristics, the highest area under the curve equal to 0.906 was obtained for miR-357 and indicates a very good diagnostic properties of this biomarker. We found expression level of mir-34a not related with PCa.

          Conclusions

          Our results support previous findings on the possibility of discriminating prostate cancer patients from healthy controls by detecting miRNA (miR-141-3p, miR-21, and miR-375). Further insights into miRNA abundance and characteristics are necessary to validate the panel of miRNA as surrogate markers in diagnosis of prostate cancer.

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          Most cited references20

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          MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer

          Dysregulation of microRNAs (miRNAs) is involved in the initiation and progression of several human cancers, including breast cancer (BC), as strong evidence has been found that miRNAs can act as oncogenes or tumor suppressor genes. This review presents the state of the art on the role of miRNAs in the diagnosis, prognosis, and therapy of BC. Based on the results obtained in the last decade, some miRNAs are emerging as biomarkers of BC for diagnosis (i.e., miR-9, miR-10b, and miR-17-5p), prognosis (i.e., miR-148a and miR-335), and prediction of therapeutic outcomes (i.e., miR-30c, miR-187, and miR-339-5p) and have important roles in the control of BC hallmark functions such as invasion, metastasis, proliferation, resting death, apoptosis, and genomic instability. Other miRNAs are of interest as new, easily accessible, affordable, non-invasive tools for the personalized management of patients with BC because they are circulating in body fluids (e.g., miR-155 and miR-210). In particular, circulating multiple miRNA profiles are showing better diagnostic and prognostic performance as well as better sensitivity than individual miRNAs in BC. New miRNA-based drugs are also promising therapy for BC (e.g., miR-9, miR-21, miR34a, miR145, and miR150), and other miRNAs are showing a fundamental role in modulation of the response to other non-miRNA treatments, being able to increase their efficacy (e.g., miR-21, miR34a, miR195, miR200c, and miR203 in combination with chemotherapy).
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            Haemolysis during Sample Preparation Alters microRNA Content of Plasma

            The presence of cell-free microRNAs (miRNAs) has been detected in a range of body fluids. The miRNA content of plasma/serum in particular has been proposed as a potential source of novel biomarkers for a number of diseases. Nevertheless, the quantification of miRNAs from plasma or serum is made difficult due to inefficient isolation and lack of consensus regarding the optimal reference miRNA. The effect of haemolysis on the quantification and normalisation of miRNAs in plasma has not been investigated in great detail. We found that levels of miR-16, a commonly used reference gene, showed little variation when measured in plasma samples from healthy volunteers or patients with malignant mesothelioma or coronary artery disease. Including samples with evidence of haemolysis led to variation in miR-16 levels and consequently decreased its ability to serve as a reference. The levels of miR-16 and miR-451, both present in significant levels in red blood cells, were proportional to the degree of haemolysis. Measurements of the level of these miRNAs in whole blood, plasma, red blood cells and peripheral blood mononuclear cells revealed that the miRNA content of red blood cells represents the major source of variation in miR-16 and miR-451 levels measured in plasma. Adding lysed red blood cells to non-haemolysed plasma allowed a cut-off level of free haemoglobin to be determined, below which miR-16 and miR-451 levels displayed little variation between individuals. In conclusion, increases in plasma miR-16 and miR-451 are caused by haemolysis. In the absence of haemolysis the levels of both miR-16 and miR-451 are sufficiently constant to serve as normalisers.
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              Moving toward System Genetics through Multiple Trait Analysis in Genome-Wide Association Studies

              Association studies are a staple of genotype–phenotype mapping studies, whether they are based on single markers, haplotypes, candidate genes, genome-wide genotypes, or whole genome sequences. Although genetic epidemiological studies typically contain data collected on multiple traits which themselves are often correlated, most analyses have been performed on single traits. Here, I review several methods that have been developed to perform multiple trait analysis. These methods range from traditional multivariate models for systems of equations to recently developed graphical approaches based on network theory. The application of network theory to genetics is termed systems genetics and has the potential to address long-standing questions in genetics about complex processes such as coordinate regulation, homeostasis, and pleiotropy.
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                Author and article information

                Contributors
                +48 17 865 1759 , eciszkow@prz.edu.pl
                Journal
                Int Urol Nephrol
                Int Urol Nephrol
                International Urology and Nephrology
                Springer Netherlands (Dordrecht )
                0301-1623
                1573-2584
                16 July 2018
                16 July 2018
                2018
                : 50
                : 9
                : 1619-1626
                Affiliations
                [1 ]Department of Urology, Municipal Hospital Rzeszow, 4 Rycerska Street, 35-241 Rzeszow, Poland
                [2 ]ISNI 0000 0001 1103 8934, GRID grid.412309.d, Department of Biotechnology and Bioinformatics, Faculty of Chemistry, , Rzeszow University of Technology, ; 6 Powstańców Warszawy Street, 35-503 Rzeszow, Poland
                Author information
                http://orcid.org/0000-0003-3401-2264
                Article
                1938
                10.1007/s11255-018-1938-2
                6133127
                30014459
                c347e0e9-bee1-426e-85c7-5562a5181c27
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 20 April 2018
                : 11 July 2018
                Categories
                Urology - Original Paper
                Custom metadata
                © Springer Nature B.V. 2018

                Nephrology
                prostate cancer,diagnosis,biomarkers,mirna
                Nephrology
                prostate cancer, diagnosis, biomarkers, mirna

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