Circulating miRNA Signature as a Potential Biomarker for the Prediction of Analgesic Efficacy of Hydromorphone.
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ABSTRACT:
SUBMITTER: Kiyosawa N
PROVIDER: S-EPMC6480077 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND: Lung adenocarcinoma is a heterogernous disease that creates challenges for classification and management. The purpose of this study is to identify specific miRNA markers closely associated with the survival of LUAD patients from a large dataset of significantly altered miRNAs, and to assess the prognostic value of this miRNA expression profile for OS in patients with LUAD. METHODS: We obtained miRNA expression profiles and corresponding clinical information for 372 LUAD patients from The Cancer Genome Atlas (TCGA), and identified the most significantly altered miRNAs between tumor and normal samples. Using survival analysis and supervised principal components method, we identified an eight-miRNA signature for the prediction of overall survival (OS) of LUAD patients. The relationship between OS and the identified miRNA signature was self-validated in the TCGA cohort (randomly classified into two subgroups: n?=?186 for the training set and n?=?186 for the testing set). Survival receiver operating characteristic (ROC) analysis was used to assess the performance of survival prediction. The biological relevance of putative miRNA targets was also analyzed using bioinformatics. RESULTS: Sixteen of the 111 most significantly altered miRNAs were associated with OS across different clinical subclasses of the TCGA-derived LUAD cohort. A linear prognostic model of eight miRNAs (miR-31, miR-196b, miR-766, miR-519a-1, miR-375, miR-187, miR-331 and miR-101-1) was constructed and weighted by the importance scores from the supervised principal component method to divide patients into high- and low-risk groups. Patients assigned to the high-risk group exhibited poor OS compared with patients in the low-risk group (hazard ratio [HR]?=?1.99, P <0.001). The eight-miRNA signature is an independent prognostic marker of OS of LUAD patients and demonstrates good performance for predicting 5-year OS (Area Under the respective ROC Curves [AUC]?=?0.626, P?=?0.003), especially for non-smokers (AUC?=?0.686, P?=?0.023). CONCLUSIONS: We identified an eight-miRNA signature that is prognostic of LUAD. The miRNA signature, if validated in other prospective studies, may have important implications in clinical practice, in particular identifying a subgroup of patients with LUAD who are at high risk of mortality.
| S-EPMC4062505 | biostudies-other
Project description:ObjectiveWith the growing incidence of ischemic stroke worldwide, there is an urgent need to identify blood biomarkers for ischemic stroke patients. Thus, our aim was to identify potential circulating microRNA (miRNA) as a potential biomarker and to explore its potential mechanism for ischemic stroke in rats.MethodsThe mRNA dataset GSE97537 and miRNA dataset GSE97532 were downloaded from the Gene Expression Omnibus (GEO) GSE97537 including 7 middle cerebral artery occlusion (MCAO) rat brain tissues and 5 sham-operated rat brain tissues GSE97532 including 6 MCAO rat blood samples and 3 sham-operated rat blood samples. Differentially expressed mRNAs and miRNAs with corrected p value ≤ 0.01 and fold change ≥2 or ≤0.05 were identified. To explore potential biological processes and pathways of differentially expressed mRNAs, functional enrichment analysis was performed. The target mRNAs of differentially expressed miRNAs were predicted using DNA Intelligent Analysis (DIANA)-microT tools. The target mRNAs and differentially expressed mRNAs were intersected.Results1228 differentially expressed mRNAs in MCAO rat brain tissues were identified. Highly expressed mRNAs were mainly enriched in the inflammatory responses. Nine differentially expressed miRNAs were identified in MCAO rat blood samples. A total of 673 target mRNAs were predicted to significantly bind these differentially expressed miRNAs. Among them, 54 target mRNAs were differentially expressed in MCAO rat blood samples. Enrichment analysis results showed that these 54 target mRNAs were closely related to neurological diseases and immune responses. Among all miRNA-mRNA relationship, miR-3552-CASP3 interaction was identified, indicating that CASP3 might be mediated by miR-3552. Functional enrichment analysis revealed that CASP3 was involved in the apoptosis pathway, indicating that miR-3552 might participate in apoptosis by CASP3.ConclusionOur findings reveal that circulating miR-3552 shows promise as a potential biomarker for ischemic stroke in rats.
| S-EPMC7381948 | biostudies-literature
Project description:BackgroundGlioma is the most common form of primary malignant intracranial tumor.MethodsIn the current study, miRNA matrix were obtained from the Chinese Glioma Genome Atlas (CGGA), and then univariate Cox regression analysis and Lasso regression analysis were utilized to select candidate miRNAs and multivariate Cox regression analysis was applied to establish a miRNA signature for predicting overall survival (OS) of glioma. The signature was assessed with the area under the curve (AUC) of the receiver operating characteristic curve (ROC) and validated by data from Gene Expression Omnibus (GEO).ResultsEight miRNAs (miR-1246, miR-148a, miR-150, miR-196a, miR-338-3p, miR-342-5p, miR-548h and miR-645) were included in the miRNA signature. The AUC of ROC analysis for 1- and 3-year OS in the CGGA dataset was 0.747 and 0.905, respectively. In the GEO dataset, The AUC for 1- and 3-year was 0.736 and 0.809, respectively. The AUC in both the CGGA and GEO datasets was similar to that based on WHO 2007 classification (0.736 and 0.799) and WHO 2016 classification (0.663 and 0.807). Additionally, Kaplan-Meier plot revealed that high-risk score patients had a poorer clinical outcome. Multivariate Cox regression analysis suggested that the miRNA signature was an independent prognosis-related factor [HR: 6.579, 95% CI [1.227-35.268], p = 0.028].ConclusionOn the whole, in the present study, based on eight miRNAs, a novel prognostic signature was developed for predicting the 1- and 3- year survival rate in glioma. The results may be conducive to predict the precise prognosis of glioma and to elucidate the underlying molecular mechanisms. However, further experimental researches of miRNAs are needed to validate the findings of this study.
| S-EPMC7528815 | biostudies-literature
Project description:BackgroundManaging acute pain in buprenorphine-maintained individuals in emergency or perioperative settings is a significant challenge. This study compared analgesic and abuse liability effects of adjunct hydromorphone and buprenorphine using quantitative sensory testing, a model of acute clinical pain, in persons maintained on 12 to 16 mg sublingual buprenorphine/naloxone.MethodsParticipants (N = 13) were enrolled in a randomized within-subject, double-blind, placebo-controlled three-session experiment. Each session used a cumulative dosing design with four IV injections (4, 4, 8, and 16 mg of hydromorphone or 4, 4, 8, and 16 mg of buprenorphine); quantitative sensory testing and abuse liability assessments were measured at baseline and after each injection. The primary analgesia outcome was change from baseline cold pressor testing; secondary outcomes included thermal and pressure pain testing, as well as subjective drug effects and adverse events.ResultsA significant two-way interaction between study drug condition and dose was exhibited in cold pressor threshold (F10,110 = 2.14, P = 0.027) and tolerance (F10,110 = 2.69, P = 0.006). Compared to after placebo, participants displayed increased cold pressor threshold from baseline after cumulative doses of 32 mg of IV hydromorphone (means ± SD) (10 ± 14 s, P = 0.035) and 32 mg of buprenorphine (3 ± 5 s, P = 0.0.39) and in cold pressor tolerance after cumulative doses of 16 mg (18 ± 24 s, P = 0.018) and 32 mg (48 ± 73 s, P = 0.041) IV hydromorphone; cold pressor tolerance scores were not significant for 16 mg (1 ± 15 s, P = 0.619) or 32 mg (7 ± 16 s, P = 0.066) buprenorphine. Hydromorphone and buprenorphine compared with placebo showed greater ratings on subjective measures of high, any drug effects, good effects, and drug liking. Adverse events were more frequent during the hydromorphone compared with buprenorphine and placebo conditions for nausea, pruritus, sedation, and vomiting.ConclusionsIn this acute clinical pain model, high doses of IV hydromorphone (16 to 32 mg) were most effective in achieving analgesia but also displayed higher abuse liability and more frequent adverse events. Cold pressor testing was the most consistent measure of opioid-related analgesia.
| S-EPMC6295244 | biostudies-literature
Project description:Ground based research modalities of microgravity have been proposed as innovative methods to investigate the aetiology of chronic age-related conditions such as cardiovascular disease. Dry Immersion (DI), has been effectively used to interrogate the sequelae of physical inactivity (PI) and microgravity on multiple physiological systems. Herein we look at the causa et effectus of 3-day DI on platelet phenotype, and correlate with both miRomic and circulating biomarker expression. The miRomic profile of platelets is reflective of phenotype, which itself is sensitive and malleable to the exposome, undergoing responsive transitions in order to fulfil platelets role in thrombosis and haemostasis. Heterogeneous platelet subpopulations circulate at any given time, with varying degrees of sensitivity to activation. Employing a DI model, we investigate the effect of acute PI on platelet function in 12 healthy males. 3-day DI resulted in a significant increase in platelet count, plateletcrit, platelet adhesion, aggregation, and a modest elevation of platelet reactivity index (PRI). We identified 15 protein biomarkers and 22 miRNA whose expression levels were altered after DI. A 3-day DI model of microgravity/physical inactivity induced a prothrombotic platelet phenotype with an unique platelet miRNA signature, increased platelet count and plateletcrit. This correlated with a unique circulating protein biomarker signature. Taken together, these findings highlight platelets as sensitive adaptive sentinels and functional biomarkers of epigenetic drift within the cardiovascular compartment.
| S-EPMC8578674 | biostudies-literature
Project description:Breast cancer (BC) is one of the most commonly diagnosed cancers worldwide. As key regulatory molecules in several biological processes, microRNAs (miRNAs) are potential biomarkers for cancer. Understanding the miRNA markers that can detect BC may improve survival rates and develop new targeted therapeutic strategies. To identify a circulating miRNA signature for diagnostic prediction in patients with BC, we developed an evolutionary learning-based method called BSig. BSig established a compact set of miRNAs as potential markers from 1280 patients with BC and 2686 healthy controls retrieved from the serum miRNA expression profiles for the diagnostic prediction. BSig demonstrated outstanding prediction performance, with an independent test accuracy and area under the receiver operating characteristic curve were 99.90% and 0.99, respectively. We identified 12 miRNAs, including hsa-miR-3185, hsa-miR-3648, hsa-miR-4530, hsa-miR-4763-5p, hsa-miR-5100, hsa-miR-5698, hsa-miR-6124, hsa-miR-6768-5p, hsa-miR-6800-5p, hsa-miR-6807-5p, hsa-miR-642a-3p, and hsa-miR-6836-3p, which significantly contributed towards diagnostic prediction in BC. Moreover, through bioinformatics analysis, this study identified 65 miRNA-target genes specific to BC cell lines. A comprehensive gene-set enrichment analysis was also performed to understand the underlying mechanisms of these target genes. BSig, a tool capable of BC detection and facilitating therapeutic selection, is publicly available at https://github.com/mingjutsai/BSig.
| S-EPMC10894035 | biostudies-literature
Project description:MicroRNAs as cancer biomarkers in serum, plasma, and other body fluids are often used but analysis of miRNA in urine is limited. We investigated the expression of selected miRNAs in the paired urine, serum, cervical scrape, and tumor tissue specimens from the women with cervical precancer and cancer with a view to identify if urine miRNAs could be used as reliable non-invasive biomarkers for an early diagnosis and prognosis of cervical cancer. Expression of three oncomiRs (miR-21, miR-199a, and miR-155-5p) and three tumor suppressors (miR-34a, miR-145, and miR-218) as selected by database search in cervical pre-cancer, cancer, and normal controls including cervical cancer cell lines were analyzed using qRT-PCR. The expression of miRNAs was correlated with various clinicopathological parameters, including HPV infection and survival outcome. We observed a significant overexpression of the oncomiRs and the downregulation of tumor suppressor miRNAs. A combination of miR-145-5p, miR-218-5p, and miR-34a-5p in urine yielded 100% sensitivity and 92.8% specificity in distinguishing precancer and cancer patients from healthy controls and it well correlates with those of serum and tumor tissues. The expression of miR-34a-5p and miR-218-5p were found to be independent prognostic factors for the overall survival of cervical cancer patients. We conclude that the evaluation of the above specific miRNA expression in non-invasive urine samples may serve as a reliable biomarker for early detection and prognosis of cervical cancer.
| S-EPMC8121812 | biostudies-literature
Project description:The aim of this study was to identify circulating microRNAs (miRNAs) that could be used as biomarkers in patients at risk for or affected by AIDS-Kaposi's sarcoma (KS). Screening of 377 miRNAs was performed using low-density arrays in pooled plasma samples of 10 HIV/human herpesvirus 8 (HHV8)-infected asymptomatic and 10 AIDS-KS patients before and after successful combined antiretroviral therapy (cART). MiR-375 was identified as a potential marker of active KS, being the most down-regulated in AIDS-KS patients after cART and the most up-regulated in naïve AIDS-KS patients compared to naïve asymptomatic subjects. Validation on individual plasma samples confirmed that miR-375 levels were higher in AIDS-KS compared to asymptomatic patients, decreased after cART-induced remission in most AIDS-KS patients and increased in patients with active KS. In asymptomatic patients miR-375 was up-regulated after cART in both screening and validation. Statistical analyses revealed an association between miR-375 changes and CD4 cell counts, which could explain the discordant cases and the opposite trend between asymptomatic and AIDS-KS patients. These data suggest that circulating miR-375 might be a good indicator of active AIDS-KS. Moreover, changes in miR-375 levels may have a prognostic value in HIV/HHV8-infected patients undergoing treatment. Further large-scale validation is needed.
| S-EPMC6349189 | biostudies-literature
Project description:Extensive effort has been put on miRNA expression signatures in epithelial ovarian cancer (EOC). Unfortunately, consistent conclusion rarely yielded from diverse studies, mainly due to the high inter-lab variability and small sample sizes. To overcome above limitations, an integrated analysis of miRNA expression signature was performed by employing Robust Rank Aggregation (RRA) method. Diagnostic analysis, Kaplan-Meier survival curves and pathway enrichment analysis were used to investigate the clinical values and biological functions of meta-signature miRNAs. A total of 519 EOC and 248 noncancerous samples were included. Seven mostly dysregulated miRNAs were identified by RRA method and two miRNAs (miR-200a-3p and miR-200c-3p) remained statistically significant after Bonferroni-correction. Diagnostic meta-analysis showed reliable diagnostic capacity of miR-200a-3p (with a pooled sensitivity of 0.84 and specificity of 0.83) and miR-200c-3p (with a pooled sensitivity of 0.75 and specificity of 0.66) for EOC. Pathway enrichment analysis and expression correlation analysis suggested miR-200a/c might contribute EOC progression by affecting cellular adhesion process. Kaplan-Meier survival analysis based on two independent cohorts revealed a strong association between miR-200a/c and overall survival in EOC patients. miR-200a/c was identified as the mostly dysregulated miRNAs in EOC and might be novel diagnostic and prognostic biomarkers for patients with EOC.
| S-EPMC5348417 | biostudies-literature
Project description:There is increasing evidence to suggest that miRNAs play an important role in predicting cancer survival. To identify a panel of miRNA signature that can divided tumor from normal bladder using miRNA expression levels, and to assess the prognostic value of this specific miRNA markers in bladder cancer (BCa).A comprehensive meta-review of published miRNA expression profiles that compared BCa and adjacent normal tissues was performed to determine candidate miRNAs as prognostic biomarkers for BCa. Vote-counting strategy and Robust Rank Aggregation method were used to identify significant meta-signature miRNAs.We identified an eight-miRNA signature including three upregulated (miR-141, miR-200c, miR-21) and five downregulated (miR-145, miR-125, miR-199a, let-7c and miR-99a) miRNAs for the prediction of overall survival (OS) using TCGA dataset, and validated in our 48 BCa patients. X-tile plot was used to generate the optimum cut-off point and Kaplan-Meier method was used to calculate OS. A linear prognostic model of eight miRNAs was constructed and weighted by the importance scores from the supervised principal component method to divide patients into high- and low-risk groups. Patients assigned to the high-risk group were associated with poor OS compared with patients in the low-risk group (HR?=?5.21, p?<?0.001). Our validation cohort of 48 patients confirmed the panel of 8-miRNAs as a reliable prognostic tool for OS in patients with BCa (HR?=?5.04, p?<?0.001).The present meta-analysis identified eight highly significant and consistently dysregulated miRNAs from 19 datasets. We also constructed an eight-miRNA signature which provided predictive and prognostic value that complements traditional clinicopathological risk factors.
| S-EPMC4508815 | biostudies-literature