Potential Diagnostic and Monitoring Biomarkers of Obstructive Sleep Apnea-Umbrella Review of Meta-Analyses.
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SUBMITTER: Fiedorczuk P
PROVIDER: S-EPMC9821668 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
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Potential Diagnostic and Monitoring Biomarkers of Obstructive Sleep Apnea-Umbrella Review of Meta-Analyses.
Fiedorczuk Piotr P Polecka Agnieszka A Walasek Marzena M Olszewska Ewa E
Journal of clinical medicine 20221221 1
Obstructive sleep apnea (OSA) is a prevalent, underdiagnosed disease that imposes a significant impact on the health and wellbeing of patients and a financial burden on individuals, their families, and society. Development of new methods of testing other than an overnight sleep study, such as measurement of serum or plasma biomarkers, may provide an easier diagnostic process to identify patients with OSA and allow earlier initiation of treatment, which might prevent serious comorbidities. We con ...[more]
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Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-M-NM-:B pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder. Total RNA from visceral fat of 18 subjects (10 OSA, 8 Control) was hybridized to 18 Affymetrix Genechip Human Gene 1.0 ST microarrays.
2012-09-01 | E-GEOD-38792 | biostudies-arrayexpress
Project description:Rationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses. Methods: Patients scheduled to undergo ventral hernia repair surgery were recruited to wear a portable home sleep monitor for two nights prior to surgery. Visceral fat biopsies were obtained intra-operatively. RNA was extracted and whole-genome expression profiling was performed. Gene Set Enrichment Analysis (GSEA) was used to identify curated gene sets that were differentially enriched in OSA subjects. Network analysis was applied to a select set of highly enriched pathways. Results: 10 patients with OSA and 8 control subjects were recruited. There were no differences in age, gender, body mass index between the two groups, but the OSA subjects had a significantly higher respiratory disturbance index (19.2 vs. 0.6, P-value 0.05) and worse hypoxemia (minimum oxygen saturation 79.7% vs. 87.8%, P-value < 0.001). GSEA identified a number of gene sets up-regulated in adipose tissue of OSA patients including the pro-inflammatory NF-κB pathway and the proteolytic ubiquitin/proteasome module. A critical metabolic pathway, the peroxisome proliferator-activated receptor (PPAR), was down-regulated in subjects with OSA. Network analysis linked members of these modules together and identified regulatory hubs. Conclusions: OSA is associated with alterations in visceral fat gene expression. Pathway-based network analysis highlighted perturbations in several key pathways whose coordinated interactions may contribute to the metabolic dysregulation observed in this complex disorder.
2012-09-01 | GSE38792 | GEO
Project description:AbstractObstructive sleep apnea (OSA) is a common chronic disease and increases the risk of cardiovascular disease, metabolic and neuropsychiatric disorders, resulting in a considerable socioeconomic burden. This study aimed to identify potential key genes influence the mechanisms and consequences of OSA.Gene expression profiles related to OSA were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in subcutaneous adipose tissues from OSA compared with normal tissues were screened using R software, followed by gene ontology (GO) and pathway enrichment analyses. Subsequently, a protein-protein interaction (PPI) network for these DEGs was constructed by STRING, and key hub genes were extracted from the network with plugins in Cytoscape. The hub genes were further validated in another GEO dataset and assessed by receiver operating characteristic (ROC) analysis and Pearson correlation analysis.There were 373 DEGs in OSA samples in relative to normal controls, which were mainly associated with olfactory receptor activity and olfactory transduction. Upon analyses of the PPI network, GDNF, SLC2A2, PRL, and SST were identified as key hub genes. Decreased expression of the hub genes was association with OSA occurrence, and exhibited good performance in distinguishing OSA from normal samples based on ROC analysis. Besides, the Pearson method revealed a strong correlation between hub genes, which indicates that they may act in synergy, contributing to OSA and related disorders.This bioinformatics research identified 4 hub genes, including GDNF, SLC2A2, PRL, and SST which may be new potential biomarkers for OSA and related disorders.
| S-EPMC7850694 | biostudies-literature
Project description:BackgroundObstructive sleep apnea (OSA) is highly prevalent, but frequently undiagnosed. The existing biomarkers of OSA are relatively insensitive and inaccurate. Long non-coding RNAs (lncRNAs) have no protein-coding ability but have a role in regulating gene expression. They are stably expressed in exosomes, easily and rapidly measurable. Changes in expression of exosomal lncRNAs can be useful for disease diagnoses. However, there are few reports on the association of exosomal lncRNAs with OSA. We aimed to investigate the exosomal lncRNA profiles to establish the differences between non-OSA, OSA with or without hypertension (HTN) and serve as a potential diagnostic biomarker.MethodsThis diagnostic test included 63 participants: [normal control (NC) =25], (OSA =23), and (HTN-OSA =15). Expression profiling of lncRNAs in isolated exosomes was performed through high-throughput sequencing in 9 participants. Subsequently, OSA/HTN-OSA related lncRNAs were selected for validation by droplet digital polymerase chain reaction (ddPCR), receiver operating characteristic (ROC) curves were used to determine the diagnostic value. The reliabilities of the screened gene were further validated in another independent cohort: (NC =10), (OSA mild =10), (OSA moderate =11), and (OSA severe =10), the correlation between clinical features and its expression was analyzed. The MiRanda software was used to predict the binding sites of interaction between microRNA (miRNA) and target genes regulated by screened lncRNA.ResultsWe identified the differentially expressed lncRNAs and mRNAs in plasma exosomes of the NC, OSA, HTN-OSA groups. Most pathways enriched in differentially expressed lncRNAs and mRNAs had previously been linked to OSA. Among them, ENST00000592016 enables discrimination between NC and OSA individuals [area under curve (AUC) =0.846, 95% confidence interval (CI): 0.72-0.97]. The severity of OSA was associated with changes in the ENST00000592016 expression. Furthermore, ENST00000592016 affected the PI3K-Akt, MAPK, and TNF pathways by regulating miRNA expressions.ConclusionsThis is the first report about differential expression of lncRNA in OSA and HTN-OSA exosomes. ENST00000592016 enables discrimination between NC and OSA individuals. This work enabled characterization of OSA and provided the preliminary work for the study of biomarker of OSA.
| S-EPMC9511177 | biostudies-literature
Project description:Although obstructive sleep apnea (OSA) patients are at high risk of developing cardiovascular disease (CVD), only a small proportion is currently diagnosed. To explore and identify the differentially expressed proteins/peptides of OSA patients with CVDs, a mass spectrometry-based salivary analysis was performed. In our study, eleven peaks were observed differentially expressed in saliva from the non-CVD and CVD groups. Five masses mass peaks (1594.1, 1673.7, 1196.6, 1290.5, and 1447.0 Da) showed an upregulated trend in the CVD group, whereas six mass peaks (3038.6, 2164.3, 2301.4, 3195.0, 2628.4, and 1721.9 Da) were downregulated in the CVD group. In addition, the alpha-2-HS-glycoprotein (AHSG) levels in saliva were verified to be decreased in CVD group compared to non-CVD group. Analysis of the salivary peptidome provides a promising approach to screening for novel biomarkers before further identification, and may contribute to early diagnosis of CVD patients with OSA.
| S-EPMC4231342 | biostudies-other
Project description:The overall validity of biomarkers in the diagnosis of obstructive sleep apnea (OSA) remains unclear. We conducted a scoping review to provide assessments of biomarkers characteristics in the context of obstructive sleep apnea (OSA) and to identify gaps in the literature. A scoping review of studies in humans without age restriction that evaluated the potential diagnostic value of biological markers (blood, exhaled breath condensate, salivary, and urinary) in the OSA diagnosis was undertaken. Retained articles were those focused on the identification of biomarkers in subjects with OSA, the latter being confirmed with a full overnight or home-based polysomnography (PSG). Search strategies for six different databases were developed. The methodology of selected studies was classified using an adaptation of the evidence quality criteria from the American Academy of Pediatrics. Additionally the biomarkers were classified according to their potential clinical application. We identified 572 relevant studies, of which 117 met the inclusion criteria. Eighty-two studies were conducted in adults, 34 studies involved children, and one study had a sample composed of both adults and children. Most of the studies evaluated blood biomarkers. Potential diagnostic biomarkers were found in nine pediatric studies and in 58 adults studies. Only nine studies reported sensitivity and specificity, which varied substantially from 43% to 100%, and from 45% to 100%, respectively. Studies in adults have focused on the investigation of IL-6, TNF-α and hsCRP. There was no specific biomarker that was tested by a majority of authors in pediatric studies, and combinatorial urine biomarker approaches have shown preliminary promising results. In adults IL-6 and IL-10 seem to have a favorable potential to become a good biomarker to identify OSA.
| S-EPMC4447611 | biostudies-literature
Project description:Untreated and long-lasting obstructive sleep apnea (OSA) may lead to important vascular abnormalities, including endothelial cell (EC) dysfunction, hypertension, and atherosclerosis. We observed a correlation between microcirculatory reactivity and endothelium-dependent release of nitric oxide in OSA patients. Therefore, we hypothesized that OSA affects (micro)vasculature and we aimed to identify vascular gene targets of OSA that could possibly serve as reliable biomarkers of severity of the disease and possibly of vascular risk. Using quantitative RT-PCR, we evaluated gene expression in skin biopsies of OSA patients, mouse aortas from animals exposed to 4-week intermittent hypoxia (IH; rapid oscillations in oxygen desaturation and reoxygenation), and human dermal microvascular (HMVEC) and coronary artery endothelial cells (HCAEC) cultured under IH. We demonstrate a significant upregulation of endothelial nitric oxide synthase (eNOS), tumor necrosis factor-alpha-induced protein 3 (TNFAIP3; A20), hypoxia-inducible factor 1 alpha (HIF-1??? and vascular endothelial growth factor (VEGF) expression in skin biopsies obtained from OSA patients with severe nocturnal hypoxemia (nadir saturated oxygen levels [SaO2]<75%) compared to mildly hypoxemic OSA patients (SaO2 75%-90%) and a significant upregulation of vascular cell adhesion molecule 1 (VCAM-1) expression compared to control subjects. Gene expression profile in aortas of mice exposed to IH demonstrated a significant upregulation of eNOS and VEGF. In an in vitro model of OSA, IH increased expression of A20 and decreased eNOS and HIF-1? expression in HMVEC, while increased A20, VCAM-1 and HIF-1?expression in HCAEC, indicating that EC in culture originating from distinct vascular beds respond differently to IH stress. We conclude that gene expression profiles in skin of OSA patients may correlate with disease severity and, if validated by further studies, could possibly predict vascular risk in OSA patients.
| S-EPMC3726633 | biostudies-literature
Project description:Next Generation Sequencing (NGS) was carried out on subjects who visited an oriental medicine clinic due to recurrent sleep disturbance, and 40 individuals (17 male and 23 female) were set as the sleep diorder (SD) group based on their scores on the sleep distrurbance questionnaire of Pittsburgh sleep quality index (PSQI). The control group consisted of 40 healthy individuals (20 males and females each), as assessed by both subjective diagnosis and test for metabolic syndrome factors.Ten individuals (five males and females each) from the SD and the control group, respectively, were allocated for NGS analysis.
2021-07-07 | GSE165041 | GEO
Project description:ObjectivesTo assess the diagnostic utility of smartphone-based measurement in detecting moderate to severe obstructive sleep apnea syndrome (OSAS).MethodsSix databases were thoroughly reviewed. Random-effect models were used to estimate the summary sensitivity, specificity, negative predictive value, positive predictive value, diagnostic odds ratio, summary receiver operating characteristic curve and measured the areas under the curve. To assess the accuracy and precision, pooled mean difference and standard deviation of apnea hypopnea index (AHI) between smartphone and polysomnography (95% limits of agreement) across studies were calculated using the random-effects model. Study methodological quality was evaluated using the QUADAS-2 tool.ResultsEleven studies were analyzed. The smartphone diagnostic odds ratio for moderate-to-severe OSAS (apnea/hypopnea index > 15) was 57.3873 (95% confidence interval [CI]: [34.7462; 94.7815]). The area under the summary receiver operating characteristic curve was 0.917. The sensitivity, specificity, negative predictive value, and positive predictive value were 0.9064 [0.8789; 0.9282], 0.8801 [0.8227; 0.9207], 0.9049 [0.8556; 0.9386], and 0.8844 [0.8234; 0.9263], respectively. We performed subgroup analysis based on the various OSAS detection methods (motion, sound, oximetry, and combinations thereof). Although the diagnostic odds ratios, specificities, and negative predictive values varied significantly (all p < 0.05), all methods afforded good sensitivity (> 80%). The sensitivities and positive predictive values were similar for the various methods (both p > 0.05). The mean difference with standard deviation in the AHI between smartphone and polysomnography was -0.6845 ± 1.611 events/h [-3.8426; 2.4735].ConclusionsSmartphone could be used to screen the moderate-to-severe OSAS. The mean difference between smartphones and polysomnography AHI measurements was small, though limits of agreement was wide. Therefore, clinicians should be cautious when making clinical decisions based on these devices.
| S-EPMC9119483 | biostudies-literature
Project description:Study objectivesTo examine episodic memory performance in individuals with obstructive sleep apnea (OSA).DesignMeta-analysis was used to synthesize results from individual studies examining the impact of OSA on episodic memory performance. The performance of individuals with OSA was compared to healthy controls or normative data.ParticipantsForty-two studies were included, comprising 2,294 adults with untreated OSA and 1,364 healthy controls. Studies that recorded information about participants at baseline prior to treatment interventions were included in the analysis.MeasurementsPARTICIPANTS WERE ASSESSED WITH TASKS THAT INCLUDED A MEASURE OF EPISODIC MEMORY: immediate recall, delayed recall, learning, and/or recognition memory.ResultsThe results of the meta-analyses provide evidence that individuals with OSA are significantly impaired when compared to healthy controls on verbal episodic memory (immediate recall, delayed recall, learning, and recognition) and visuo-spatial episodic memory (immediate and delayed recall), but not visual immediate recall or visuo-spatial learning. When patients were compared to norms, negative effects of OSA were found only in verbal immediate and delayed recall.ConclusionsThis meta-analysis contributes to understanding of the nature of episodic memory deficits in individuals with OSA. Impairments to episodic memory are likely to affect the daily functioning of individuals with OSA.
| S-EPMC3543053 | biostudies-literature