miRNAs In Diagnosis Research Articles

Promises and Pitfalls of microRNAs as Biomarkers of Heart Failure

Background: MicroRNAs (miRNAs) are important non-coding molecules with regulatory roles in gene expression. In the past few years, miRNAs have arisen as apt candidates to assist with the diagnosis, prognosis and monitoring of several diseases. Cardiovascular pathologies have emerged as a particularly interesting field for miRNAs as markers, as it appears that the pathophysiological changes following heart failure lead to measurable alterations in circulating miRNA levels. Contents: In the present review, we explore the value, sensitivity and specificity of circulating miRNAs in diagnosis and prognosis of heart failure as reported in the literature, and discuss the underlying factors that currently prevent circulating miRNAs from becoming true clinical markers. In spite of the numerous attempts in identification and administration of cardiac miRNA markers, relatively small progress has been made in the application of these markers in clinical settings. Small study populations and methodological differences, among other possible etiologies, have resulted in little reproducibility among studies. Conclusion: Despite the encouraging preliminary results, considerable challenges, mainly concerning standardization, have thus far prevented miRNAs from approximating the validity of established biomarkers that are routinely used in clinics, let alone surpassing them. To conclude, rigorous methodology and universally standardized protocols prior to, and during miRNA analysis are required to warrant reproducible, validated and reliable results which will lead to clinical application of miRNA cardiac biomarkers.

Roles and applications of miRNAs in diagnosis, treatment, prognosis, and control of the parasitic diseases. Part I: Helminthes

Roles and applications of miRNAs in diagnosis, treatment, prognosis, and control of the parasitic diseases. Part I: Helminthes

Clinical Value of Circulating miRNA in Diagnosis, Prognosis, Screening and Monitoring Therapy of Pancreatic Ductal Adenocarcinoma-A Review of the Literature.

Pancreatic cancer (PC) is considered to be the seventh most common cause of cancer-related deaths. The number of deaths caused by PC is estimated to increase in the future. An early diagnosis of PC is crucial for improving treatment outcomes. The most common histopathological subtype of PC is pancreatic ductal adenocarcinoma (PDAC). MicroRNAs (miRNAs)-which are endogenous non-coding RNAs involved in the posttranscriptional regulation of multiple gene expression-constitute useful diagnostic and prognostic biomarkers in various neoplasms, including PDAC. Circulating miRNAs detected in a patient's serum or plasma are drawing more and more attention. Hence, this review aims at evaluating the clinical value of circulating miRNA in the screening, diagnosis, prognosis and monitoring of pancreatic ductal adenocarcinoma therapy.

The Potential Role of Serum and Exhaled Breath Condensate miRNAs in Diagnosis and Predicting Exacerbations in Pediatric Asthma

Asthma is the most common chronic disease of the respiratory system in children and the number of new cases is constantly increasing. It is characterized by dyspnea, wheezing, tightness in the chest, or coughing. Due to diagnostic difficulties, disease monitoring, and the selection of safe and effective drugs, it has been shown that among the youngest patients, miRNAs fulfilling the above roles can be successfully used in common clinical practice. These biomolecules, by regulating the expression of the body's genes, influence various biological processes underlying the pathogenesis of asthma, such as the inflammatory process, remodeling, and intensification of airway obstruction. They can be detected in blood serum and in exhaled breath condensate (EBC). Among children, common factors responsible for the onset or exacerbation of asthma, such as infections, allergens, air pollution, or tobacco smoke present in the home environment, cause a change the concentration of miRNAs in the body. This is related to their significant impact on the modulation of the disease process. In the following paper, we review the latest knowledge on miRNAs and their use, especially as diagnostic markers in assessing asthma exacerbation, with particular emphasis on the pediatric population.

MiRNAs role in bladder cancer pathogenesis and targeted therapy: Signaling pathways interplay - A review.

Bladder cancer (BC) is the 11th most popular cancer in females and 4th in males. A lot of efforts have been exerted to improve BC patients' care. Besides, new approaches have been developed to enhance the efficiency of BC diagnosis, prognosis, therapeutics, and monitoring. MicroRNAs (miRNAs, miRs) are small chain nucleic acids that can regulate wide networks of cellular events. They can inhibit or degrade their target protein-encoding genes. The miRNAs are either downregulated or upregulated in BC due to epigenetic alterations or biogenesis machinery abnormalities. In BC, dysregulation of miRNAs is associated with cell cycle arrest, apoptosis, proliferation, metastasis, treatment resistance, and other activities. A variety of miRNAs have been related to tumor kind, stage, or patient survival. Besides, although new approaches for using miRNAs in the diagnosis, prognosis, and treatment of BC have been developed, it still needs further investigations. In the next words, we illustrate the recent advances in the role of miRNAs in BC aspects. They include the role of miRNAs in BC pathogenesis and therapy. Besides, the clinical applications of miRNAs in BC diagnosis, prognosis, and treatment are also discussed.

Evaluation the role of MicroRNAs in diagnosis and prognosis of acute myeloid leukemia

Acute myeloid leukemia (AML) is a clonal disorder of hematopoietic progenitor cells which are characterized by relevant heterogeneity in terms of phenotypic, genotypic, and clinical features. Among the genetic aberrations that control disease development there are microRNAs (miRNAs). The present study aimed to investigate the role of miRNAs in diagnosis and prognosis of AML and it was designed as cross sectional study in patients with acute myeloid leukemia and normal individuals as control group, we determined: RNA yield and quality; and quantification of miRNA-203, miRNA-143, and miRNA-495 expression by Quantitative Real-Time PCR (qPCR) in the serum of AML patients and control groups. The study was conducted in period between December 2020 and September 2021 at the University of Babylon, College of Science, department of biology. In this case-control study, blood samples were collected from 115 AML patients (38 male and 77 female) and their ages ranged between 18 and 66 years , then, 60 patients were selected based on the quantity and natural color of their samples (28 male and 32 female), in addition to the 30 samples from healthy apparently subjects as a control group (11 male and 19 female), and this group matched with the patients groups.

Evaluation the role of MicroRNAs in diagnosis and prognosis of acute myeloid leukemia

Acute myeloid leukemia (AML) is a clonal disorder of hematopoietic progenitor cells which are characterized by relevant heterogeneity in terms of phenotypic, genotypic, and clinical features. Among the genetic aberrations that control disease development there are microRNAs (miRNAs). The present study aimed to investigate the role of miRNAs in diagnosis and prognosis of AML and it was designed as cross sectional study in patients with acute myeloid leukemia and normal individuals as control group, we determined: RNA yield and quality; and quantification of miRNA-203, miRNA-143, and miRNA-495 expression by Quantitative Real-Time PCR (qPCR) in the serum of AML patients and control groups. The study was conducted in period between December 2020 and September 2021 at the University of Babylon, College of Science, department of biology. In this case-control study, blood samples were collected from 115 AML patients (38 male and 77 female) and their ages ranged between 18 and 66 years , then, 60 patients were selected based on the quantity and natural color of their samples (28 male and 32 female), in addition to the 30 samples from healthy apparently subjects as a control group (11 male and 19 female), and this group matched with the patients groups.

PBMC miRNA in diagnosis of rheumatoid arthritis

Background and objective: RA is an autoimmune disorder mediated by autoantibodies. miRNAs have been shown to negatively regulate protein translation via an antisense RNA-RNA interaction. Altered miRNA expression has been well established in autoimmune diseases. In this study, the expression of four microRNA was analysed. Also, correlation between microRNA and immunological markers was examined. Method: RNA was isolated from PBMC obtained from 100 RA patients and age-gender matched healthy controls. Levels of mature miRNA of miR146a, miR155a, miR499 and miR124a were detected using real time PCR. Downstream cytokine was analysed using ELISA from R&D systems. Result: Real time PCR reveals that the expression of miR-146a, miR-155a, miR-499 in PBMC was found to be down regulated in RA patients when compared to the controls by fold change of 0.15, 0.69 and 0.04 respectively whereas, expression of miR124a was found to be low to detect. Expression of TNF- alpha upregulated (p-value=0.09) and IL6 was found to be insignificantly down regulated in patient. miRNA 155a was found to be in significant negative correlation with rheumatoid factor (r= -0.210; p=0.038).

The role of exosomal miRNA in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) impacts more than one-third of the population and is linked with other metabolic diseases. The term encompasses a wide spectrum of diseases, from modest steatosis to nonalcoholic steatohepatitis, fibrosis and, ultimately, cirrhosis with the potential for development of hepatocellular carcinoma. Currently, available methods for diagnosing NAFLD are invasive or lack accuracy, and monitoring to determine response to therapeutic interventions is challenging. Exosomes are nano-scaled extracellular vesicles that are secreted by a variety of cells. They convey proteins, mRNA, miRNA, and other bioactive molecules between cells and are involved in an extensive range of biological processes, particularly cell-cell communication. Several reports suggest that exosomes mediate miRNAs and, thus, they have potential clinical utility for diagnosis, prognosis, and therapeutics in liver diseases. In view of the vital role of exosomal microRNA in disease, we here synthesized current knowledge about the biogenesis of exosomal miRNA and exosome-mediated microRNA transfer. We then discuss the potential of exosomal miRNA in diagnosis and therapeutics of NAFLD.

Circulating MicroRNAs for Diagnosis of Acute Pulmonary Embolism: Still a Long Way to Go.

Venous thromboembolism (VTE) represents the third most frequent cause of acute cardiovascular syndrome. Among VTE, acute pulmonary embolism (APE) is the most life-threatening complication. Due to the low specificity of symptoms clinical diagnosis of APE may be sometimes very difficult. Accordingly, the latest European guidelines only suggest clinical prediction tests for diagnosis of APE, eventually associated with D-dimer, a biomarker burdened by a very low specificity. A growing body of evidence is highlighting the role of miRNAs in hemostasis and thrombosis. Due to their partial inheritance and susceptibility to the environmental factors, miRNAs are increasingly described as active modifiers of the classical Virchow's triad. Clinical evidence on deep venous thrombosis reported specific miRNA signatures associated to thrombosis development, organization, recanalization, and resolution. Conversely, data of miRNA profiling as a predictor/diagnostic marker of APE are still preliminary. Here, we have summarized clinical evidence on the potential role of miRNA in diagnosis of APE. Despite some intriguing insight, miRNA assay is still far from any potential clinical application. Especially, the small sample size of cohorts likely represents the major limitation of published studies, so that extensive analysis of miRNA profiles with a machine learning approach are warranted in the next future. In addition, the cost-benefit ratio of miRNA assay still has a negative impact on their clinical application and routinely test.

The High Ratio of the Plasma miR-96/miR-99b Correlated With Poor Prognosis in Patients With Metastatic Colorectal Cancer.

Object: This study aims to clarify the expression of plasma miRNA in CRC patients, and to clarify the potential use of these miRNAs in diagnosis and prognosis, and to establish a prognostic model to initially explore its clinical value. Methods: We detected the expression of 6 miRNAs in normal colon epithelial cell lines and colorectal cancer cell lines by qRT-PCR and they were validated in the tissues of three subtypes: 20 healthy subjects, 41 pCRC and 49 mCRC patients. COX regression and ROC analyses use to evaluate the diagnostic and prognostic efficacy of candidate miRNAs. Subsequently, we initially established a nomogram prognostic model. MiRNA is also used to construct miRNA-mRNA interaction network and PPI network modules. Results: Five miRNAs showed significant differential expression in pCRC, mCRC patients and normal groups. ROC analysis showed that CEA, miR-96, miR-99b and miR-96/miR-99b are distinguishable from pCRC and mCRC patients, with AUC ranging from 0.65 to 0.91; among them, the ratio of miR-96/miR-99b is stronger than any diagnostic indicators, such as CEA and CA125. Multivariate survival analysis identified miR-96, miR-99b, N stage, M stage and clinical stage as independent prognostic indicators of mCRC. The nomogram based on these 5 characteristics has satisfactory prognostic values. Conclusion: Our data indicate that plasma miR-96/miR-99b can be used as a promising biomarker for early detection of mCRC patients; our nomogram has a promising evaluation value.

P-081: A novel circulating miRNA involved in T cell senescence of multiple myeloma patients

<h3>Background</h3> Many circulating miRNAs were reported as biomarkers of multiple myeloma (MM),but the functions of these circulating miRNAs are not clarified recently. The aim of this work is to identify novel biomarkers of circulating miRNAs in diagnosis and prognosis for MM and reveal their function in the pathogenesis of MM. <h3>Methods</h3> MiRNAs profiling in serum(n=15) and MM cells(CD138+, n=10) were analyzed by RNA-sequencing of MM patients. The common dysregulated miRNAs(P<0.05) were identified via Veen Diagram analysis in serum and MM cells between MM patients and healthy donors, then validated by RT-PCR. ROC analysis and Kaplan-Meier(K-M) analysis were performed to evaluate the differently expressed circulating miRNAs in diagnosis and prognosis in MM patients, respectively. Exosomes of serum were isolated and characterized by dynamic light scattering, transmission microscopy, and western blot analysis. <h3>Results</h3> There were stable and specific miRNA expression profiles in serum and tumor cells of MM patients. The miRNA profiling of MM serum showed that there were 74 differential circulating miRNAs(P<0.05), among which 56 miRNAs(75.7%) were down-regulated and 18 miRNAs were up-regulated(24.3%). MiRNA profiling of MM cells showed that there were 376 miRNAs differentially expressed(P<0.05), of which 87(23.1%) were down-regulated and 289(76.9%) were up-regulated. Veen analysis found 36 common dysregulated miRNAs both in serum and tumor cells of MM. There were 22.3% of differential miRNAs located on chromosome 1 and 17. Five circulating miRNAs(miR-27b-3p, miR-145-3p, miR-628-3p, miR-342-5p and miR-30e-3p) were further confirmed differentially expressed in MM patients(n=201) by RT-PCR. K-M analysis showed that MM patients with low level of miR-27b, miR-145, and miR-628 had shortened PFS and OS. Strikingly, comparing to the decreased level of miR-27b in MM patients serum, miR-27b was enriched in the exosome of serum. MM patients with low level of serum miR-27b displayed lower CD3+T cells and CD3+CD4+T cells in peripheral blood. Our further study found increased proportation of senescent T cells in MM patients with low level of serum miR-27b, especially in CD8+T cells. In order to confirm T cell senescent phenotype, PBMCs were co-cultured with MM patients serum exosomes which mimic the in vivo situation. Flow cytometry analysis showed the CD28 expression was notably decreased on the CD3+ T cells in the co-culture group. In addition, RT-PCR and flow cytometry analysis showed that overexpression of miR-27b significantly down-regulated the level of CD28 in jurkat cells, a T cell line. These findings suggested an immune suppressive microenvironment in MM patients with lower level of serum miR-27b. <h3>Conclusion</h3> Circulating miRNA works as a usful biomarker in diagnosis and prognosis of MM. Strigently, serum miR-27b is a novel circulating miRNA involved in T cell senescence of multiple myeloma patients which indicated the poor outcome of patients with MM.

P–343 Identification of circulating leukocyte microRNA–125b and microRNA–142–3p expression profiles in women with endometriosis before surgery and at 1 month after surgery

Abstract Study question To investigate the expression profiles of microRNA–125b and micrpRNA–142–3p in women with endometriosis, compared with controls before surgery and at 1 month after surgery. Summary answer The over-expression of miRNA–125b and miRNA–142–3p may be involved in the aetiopathogenesis of endometriosis which is related to systemic chronic inflammation. What is known already Currently, there is no reliable non-invasive diagnostic biomarker for endometriosis. MicroRNAs (miRs) are small, non-coding RNAs that are involved in the post-transcriptional regulation of gene expression and promising biomarker candidates for noninvasive diagnosis of various diseases. Despite the small number of studies found that miRNA–125b and miRNA–142–3p have been associated with endometriosis, further evidence is therefore required from studies that examine these two miRNAs in diagnosis and even follow-up of women with endometriosis. Owing to endometriosis is a systemic chronic inflammatory disease, investigating these miRs in blood leukocytes of patients with endometriosis may illustrates the molecular mechanism of endometriosis. Study design, size, duration This is a prospective longitudinal study performed between 2018 November and 2021 February. The sample size of 42 individuals of two groups were calculated considering the power analysis (α = 0.05) with Mann-Whitney U test (effect size,d=0.8) and were calculated as 80%. Women with endometriosis (n = 21) and surgically confirmed endometriosis-free women (n = 21) were included in the study. Laparoscopy and/or laparotomy was performed to determine the presence or absence of endometriosis. Participants/materials, setting, methods Women aged 18–50 years were recruited from two tertiary hospital settings. Severity of endometriosis was assessed by the rASRM classification. Using real-time quantitative PCR, miRNA–125b and miRNA–142–3p in leukocyte were analyzed in women with endometriosis before surgery and at 1 month after surgery, compared to controls without endometriosis. The results were calculated as relative quantification values. The presumed targets of these two miRNAs were identified via 3 different target prediction algorithms:TargetScan, miRDB and DIANA-TarBase. Main results and the role of chance There were no demographic discrepancies between groups. The relative expression of miRNA–125b and miRNA–142–3p were significantly higher in women with endometriosis than in control subjects before surgery (p = 0.0001;p=0001) and at 1 month after surgery, respectively (p = 0.0001;p=0001). Despite the relative expression of miRNA–125b and miRNA–142–3p were decreased 1.75- and 2.4-fold, respectively at 1 month after surgery, we observed no significant differences in the relative expression of miRNA–125b and miRNA–142–3p between before surgery and at 1 month after surgery, respectively (p = 0.110; p = 0.910). Bioinformatic analyses of three databases showed that miRNA–142–3p expression levels were found to be closely associated with fifty-seven genes. Among these target genes, CFL2, RGL2, WASL, CRK, BNC2, CLOCK, TGFBR1, CIITA and ZNF217 were found to be associated with endometriosis. Whereas, no target gene were observed to be associated with miRNA–125b expression in common with these three databases. The ROC curves showed that the expression of miRNA–125b and microRNA–142–3p had an area under the ROC curve (AUC) of 0.77 (sensitivity 61.9%, specificity 88.1% (0.0001;95%CI 0.65–0.90)) and AUC of 0.71 (sensitivity 52.4%, specificity 73.8% (p &amp;lt; 0.007;95%CI 0.58–0.84)) before surgery, respectively. Correlational analysis showed a significant positive correlation between miRNA–142–3p and Hemoglobin A1c (Spearman’s correlation, r = 0.507;p=0.019) in the endometriosis group. Limitations, reasons for caution Further studies are needed to examine the expression of these miRs with a long-term follow up in order to increase their usefulness as a predictor in the clinical practice. It is required to identify the expressions levels of predicted target genes which are associated with endometriosis and regulated by miRNA–142–3p. Wider implications of the findings: Findings suggest that the over-expression of miRNA–125b and miRNA–142–3p may be potential mechanisms involved in the etiopathogenesis of endometriosis which is a systemic chronic inflammatory disease. We observed that miRNA–125b may be a more reliable biomarker than miRNA–142–3 for noninvasive diagnosis of endometriosis and even follow-up of women with endometriosis. Trial registration number 118S298

Detection of urinary miRNAs for diagnosis of clear cell renal cell carcinoma

The lack of symptoms at the early stages of clear cell renal cell carcinoma (ccRCC) allows the tumour to metastasize, leading to a dramatic reduction in patient survival. Therefore, we studied and set up a method based on urinary microRNAs (miRNAs) for the diagnosis of ccRCC. First, miRNA expression in ccRCC specimens and kidney tissues from healthy subjects (HSs) was investigated through analysis of data banks and validated by comparing expression of miRNAs in ccRCC and adjacent non-cancerous kidney tissue specimens by RT-qPCR. Subsequently, we developed an algorithm to establish which miRNAs are more likely to be found in the urine of ccRCC patients that indicated miR-122, miR-1271, and miR-15b as potential interesting markers. The evaluation of their levels and three internal controls in the urine of 13 patients and 14 HSs resulted in the development of a score (7p-urinary score) to evaluate the presence of ccRCC in patients. The resulting area under the Receiver Operating Characteristic (ROC) curve, sensitivity, and specificity were equal to 0.96, 100% (95% CI 75–100%), and 86% (95% CI 57–98%), respectively. In conclusion, our study provides a proof of concept that combining the expression values of some urinary miRNAs might be useful in the diagnosis of ccRCC.

Fecal MicroRNAs as Potential Biomarkers for Screening and Diagnosis of Intestinal Diseases.

MicroRNAs (miRNAs) are a class of conserved endogenous, small non-coding RNA molecules with a length of 18–25 nucleotides that regulate gene expression by RNA interference processes, including mRNA chopping, mRNA deadenylation, and translation inhibition. miRNAs maintain the physiological functions of the intestine and are instrumental in gut pathogenesis. miRNAs play an important role in intercellular communication and are present in all body fluids, including stools with different composition and concentrations. However, under diseased conditions, miRNAs are aberrantly expressed and act as negative regulators of gene expression. The stable and differentially expressed miRNAs in stool enables miRNAs to be used as potential biomarkers for screening of various intestinal diseases. In this review, we summarize the expressed miRNA profile in stool and highlight miRNAs as biomarkers with potential clinical and diagnostic applications, and we aim to address the prospects for recent advanced techniques for screening miRNA in diagnosis and prognosis of intestinal disorders.

Exosomal MicroRNAs as Liquid Biopsy Biomarkers in Hepatocellular Carcinoma.

PurposeHepatocellular carcinoma (HCC) has a high incidence in China and exploring effective ways for early diagnosis is an important method to improve the prognosis of patients with HCC. Additional studies reported that. Some kinds of microRNA (miRNA) in plasma will change accordingly during HCC progress, and this change can be used to diagnose HCC, especially with miRNA-122, miRNA-21 and miRNA-96. We were aiming at investigating the values of the exosomal miRNAs in diagnosis and prognosis for HCC patients.Patients and MethodsBlood samples from 50 patients with HCC and 50 patients with hepatic cirrhosis and 50 healthy volunteers were obtained. The diagnostic accuracy of the plasma and exosomal miRNAs and the comparisons among different groups were measured by the area under the curve (AUC) on receiver operating characteristic (ROC) curve analysis.ResultsExpression levels of miRNA-21 and miRNA-96 were significantly higher in patients with HCC and of miRNA-122 were significantly lower in HCC compared with cirrhotic patients in both exosomes and plasma. Among different groups, exosomal miRNA-122, miRNA-21 and miRNA-96 were significantly more accurate in diagnosing HCC than those miRNAs in plasma and the alpha-fetoprotein (AFP) level. The miRNA panel had high accuracy in discriminating HCC from the cirrhosis group (AUC 0.924; 95% CI; sensitivity 82%, specificity 92%) and healthy volunteers’ group. Exosomal miRNA-21 and miRNA-96 with low expression and miRNA-122 with high expression could be associated with a patient’s survival time. However, the miRNA panel could better predict the HCC patient’s survival time compared with each miRNA individually.ConclusionThis study showed that the expression levels of miRNA-122, miRNA-21 and miRNA-96 in exosomes were more significantly changed than those miRNAs in plasma in patients with HCC compared with cirrhotic patients, and the exosomal miRNA panel containing miRNA-122, miRNA-21 and miRNA-96 could be defined as a diagnostic biomarker for patients with HCC. We also conclude that different expression of exosomal miRNAs, especially the miRNA panel, could predict the HCC patient’s prognosis.

Role of MicroRNA in the Diagnosis and Management of Hepatocellular Carcinoma.

Hepatocellular Carcinoma (HCC) is one of the most common malignant tumors in the world and comes third in cancer-induced mortality. The need for improved and more specific diagnostic methods that can detect early-stage disease is immense, as it is amenable to curative modalities, while advanced HCC is associated with low survival rates. microRNA (miRNA) expression is deregulated in HCC and this can be implemented both diagnostically and therapeutically. To provide a concise review on the role of miRNA in diagnosis, prognosis, and treatment of HCC. We conducted a comprehensive review of the PubMed bibliographic database. Multiple miRNAs are involved in the pathogenesis of HCC. Measurement of the levels of these miRNAs either in tumor tissue or in the blood constitutes a promising diagnostic, as well as prognostic tool. OncomiRs are miRNAs that promote tumorigenesis, thus inhibiting them by administering antagomiRs is a promising treatment option. Moreover, replacement of the depleted miRNAs is another potential therapeutic approach for HCC. Modification of miRNA levels may also regulate sensitivity to chemotherapeutic agents. miRNA play a pivotal role in HCC pathogenesis and once the underlying mechanisms are elucidated, they will become part of everyday clinical practice against HCC.

MicroRNAs as potential biomarkers for the diagnosis of glioma: A systematic review and meta-analysis.

Glioma is the most common central nervous system tumor and associated with poor prognosis. Identifying effective diagnostic biomarkers for glioma is particularly important in order to guide optimizing treatment. MicroRNAs (miRNAs) have drawn much attention because of their diagnostic value in diverse cancers, including glioma. We summarized studies to identify the potential diagnostic values of miRNAs in glioma patients. We included articles reporting miRNAs for differentiation of glioma patients from controls. We calculated sensitivities, specificities, and area under the curves (AUC) of individual miRNA and miRNA panels. We found that overall sensitivity, specificity, and AUC of miRNAs in diagnosis of glioma were 85% (95% confidence interval [CI]: 0.81‐0.89), 90% (95% CI 0.85‐0.93), and 93% (95% CI 0.91‐0.95), respectively. Meta‐regression analysis showed that the detection of miRNAs expression in cerebrospinal fluid (CSF) and brain tissue largely improved the diagnostic accuracy. Likewise, panels of multiple miRNAs could enhance the pooled sensitivity. Moreover, AUC of miR‐21 was 0.88, with 86% sensitivity and 94% specificity. This study demonstrated that miRNAs could function as potential diagnosis markers in glioma. Detection of miRNAs in CSF and brain tissue displays high accuracy in the diagnosis of glioma.

MicroRNA Alterations in the Brain and Body Fluids of Humans and Animal Prion Disease Models: Current Status and Perspectives.

Prion diseases are transmissible progressive neurodegenerative conditions characterized by rapid neuronal loss accompanied by a heterogeneous neuropathology, including spongiform degeneration, gliosis and protein aggregation. The pathogenic mechanisms and the origins of prion diseases remain unclear on the molecular level. Even though neurodegenerative diseases, including prion diseases, represent distinct entities, their pathogenesis shares a number of features including disturbed protein homeostasis, an overload of protein clearance pathways, the aggregation of pathological altered proteins, and the dysfunction and/or loss of specific neuronal populations. Recently, direct links have been established between neurodegenerative diseases and miRNA dysregulated patterns. miRNAs are a class of small non-coding RNAs involved in the fundamental post-transcriptional regulation of gene expression. Studies of miRNA alterations in the brain and body fluids in human prion diseases provide important insights into potential miRNA-associated disease mechanisms and biomarker candidates. miRNA alterations in prion disease models represent a unique tool to investigate the cause-consequence relationships of miRNA dysregulation in prion disease pathology, and to evaluate the use of miRNAs in diagnosis as biomarkers. Here, we provide an overview of studies on miRNA alterations in human prion diseases and relevant disease models, in relation to pertinent studies on other neurodegenerative diseases.

Abstract 5402: A panel of miRNAs for diagnosis of wild-type thyroid nodules with pre-surgical indeterminate cytology

Abstract Fine-needle aspiration (FNA) cytology is the gold standard for the evaluation of thyroid nodules, but about 30% are cytologically indeterminate. The inability to resolve preoperative thyroid nodules as benign or malignant is therefore a challenge. Molecular tests in FNA are useful to assist the diagnosis and the management of patients. However, if a thyroid nodule is indeterminate and genetic tests are inconclusive, surgical excision may be considered for definitive diagnosis. To overcome these limitations, novel diagnostic procedures and molecular tests are required. Among these, miRNAs have been reported as promising molecular markers in thyroid cancer. The aim of this study was to evaluate the potential diagnostic utility of miRNA expression in preoperative diagnosis of thyroid nodules with indeterminate cytology and wild type in RAS family genes and BRAF gene. The miRNA expression profile was evaluated in a small cohort of 12 wild-type Follicular Adenomas (FAs) and 4 wild-type Infiltrative Follicular Variant of Papillary Thyroid Carcinomas (IFVPTCs) with pre-surgical indeterminate cytology or in patients with cytological diagnosis not available. The two groups have been selected with similar characteristics in terms of age of patients, nodules size and with a ratio Male-Female 1:3. The expression of 798 miRNAs has been evaluated by using nCounter Nanostring technology, a sensitive and reproducible method. The differential miRNAs expression between FAs and IFVPTCs was investigated by applying the non-parametric Mann-Whitney U-test. In addition, an unsupervised hierarchical clustering analysis by Pearson correlation was performed. We found a set of 13 miRNAs differentially expressed between malignant and benign lesions. miR-222-3p, miR-30d-5p, miR-100-5p, miR-1972, miR-125b-5p, miR-155-5p were significantly up-regulated, whereas miR-574-5p, let-7f-5p, miR-148a-3p, miR-598-3p, miR-195-5p, miR-301a-3p, miR-5196-3p+hsa-miR-6732-3p were significantly down-regulated in IFVPTCs compared to FAs (p-value&amp;lt;0,05). The unsupervised hierarchical clustering analysis has identified 2 main clusters: the first one consisted of 9 FAs, whereas the second one consisted of 4 IFVPTCs and 3 FAs. The 4 IFVPTCs are grouped in an unique sub-cluster with a correlation of 0,74. This miRNA expression profile could distinguish malignant from benign lesions. If these results will be confirmed in a wide cohort of patients and in FNA cytology, this strategy could increase the diagnostic yield and improve the preoperative diagnosis of wild-type thyroid nodules with indeterminate cytology. Although this is a preliminary study, the deregulation of this set of miRNAs might help identify malignant nodules that are negative for well-known gene alterations in preoperative FNAs. Citation Format: Maria Denaro, Vincenzo Condello, Clara Ugolini, Elisabetta Macerola, Anello Marcello Poma, Gabriele Materazzi, Paolo Vitti, Fulvio Basolo. A panel of miRNAs for diagnosis of wild-type thyroid nodules with pre-surgical indeterminate cytology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5402.