scholarly journals High-Throughput Sequencing-Based Identification of Serum Exosomal Differential miRNAs in High-Grade Glioma and Intracranial Lymphoma

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Shun Wang ◽  
Zhenkuan Xu ◽  
Chao Zhang ◽  
Rui Yu ◽  
Jun Jiang ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
High Throughput ◽  
Roc Curve ◽  
High Throughput Sequencing ◽  
High Grade Glioma ◽  
Differentially Expressed ◽  
High Grade ◽  
Healthy Controls ◽  
Exosomal Mirnas ◽  
Serum Exosomes

Objective. At present, no effective noninvasive method is currently available for the differential diagnosis of high-grade glioma and intracranial lymphoma. In the present study, we aimed to screen microRNA (miRNA) markers in serum exosomes for differential diagnosis of high-grade glioma and intracranial lymphoma using high-throughput sequencing technology. Methods. Patients with intracranial lymphoma or high-grade glioma and healthy controls were included in this study (training cohort ( n = 10 ) and validation cohort: intracranial lymphoma ( n = 10 ), high-grade glioma ( n = 32 ), and healthy controls ( n = 20 )). After RNA was extracted from serum exosomes, the high-throughput sequencing was used to determine the expression profiles of serum exosomal miRNAs and screen the differentially expressed miRNAs. RT-qPCR was used to verify the expressions of the selected miRNAs. The differences of miRNA expressions between groups were assessed by the Kruskal-Wallis test. The diagnostic value was analyzed using the receiver operating characteristic (ROC) curve. Results. High-throughput sequencing demonstrated that 170 miRNAs, including 109 upregulated ones and 61 downregulated ones, were differentially expressed in serum exosomes between the patients with intracranial lymphoma and high-grade glioma. Compared with the healthy controls, the number of differential serum exosomal miRNAs in the high-grade glioma group and intracranial lymphoma group was 130 and 173, respectively. RT-qPCR proved that both miR-766-5p and miR-376b-5p were significantly downregulated in high-grade glioma and intracranial lymphoma patients compared with the healthy controls (all p < 0.001 ), and the expression of serum exosomal miR-766-5p in the intracranial lymphoma group was lower compared with the high-grade glioma group ( p < 0.05 ). The areas under ROC curve (AUCs) of serum exosomal miR-766-5p and miR-376b-5p for the diagnosis of glioma were 0.8883 ( p < 0.001 ) and 0.7688 ( p = 0.001 ), respectively, and they were 0.9271 ( p < 0.001 ) and 0.8542 ( p < 0.001 ), respectively, for the diagnosis of intracranial lymphoma. Moreover, the AUC value of serum exosomal miR-766-5p for the differential diagnosis of glioma and intracranial lymphoma was 0.7201 ( p = 0.026 ). Conclusions. miR-766-5p and miR-376b-5p in serum exosomes might be used as auxiliary diagnostic indicators for high-grade glioma and intracranial lymphoma, and miR-766-5p might be used as a differential diagnostic marker for both diseases.

scholarly journals Serum Exosomal miRNAs as Biomarkers of Early Diagnosis and Progression in Parkinson's Disease

2021 ◽  
Author(s):  
Qian Yang ◽  
Shulei He ◽  
Lu Huang ◽  
Ci Shao ◽  
Tiejian Nie ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Diagnosis ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Healthy Controls ◽  
Qrt Pcr ◽  
Exosomal Mirnas ◽  
Serum Exosomes

Abstract BackgroundBlood-based test for disease progression and early diagnosis of Parkinson’s disease (PD) is a long awaited but unsolved key problem in the clinic. The profiles of microRNAs (miRNAs) are regarded as potential diagnostic biomarkers in human diseases whereas the miRNAs in the periphery are susceptible to the influence of various components. MiRNAs enriched in serum exosomes have revealed disease-specific advantages for the diagnosis due to their high abundance, stability and resistant to degradation. This study aimed to screen differentially expressed exosomal miRNAs between healthy controls and PD patients to aid in diagnosis. MethodsA total of 103 healthy controls and diagnosed PD patients at different Hoehn and Yahr (H&Y) stages in Tangdu Hospital were included. In total, 185 differentially expressed miRNAs were obtained through miRNA sequencing of serum exosomes as well as edgeR and t-test analyses. Subsequently, the weighted gene co-expression network analysis (WGCNA) was utilized to identify the commonly expressed miRNAs in all stages of PD by constructing connections between modules and specifically expressed miRNAs in each stage of PD by functional enrichment analysis. The obtained miRNAs were further validated by quantitative real-time polymerase chain reaction (qRT-PCR) with peripheral blood exosomes from 30 more participants. ResultsUsing WGCNA, it was found that 4 miRNAs were commonly associated with all the stages of PD and 13 miRNAs were specifically associated with different stages of PD. Among the 17 miRNAs, 2 were commonly expressed in all the stages of PD and 5 were specifically expressed in different stages of PD via qRT-PCR; 5 were also specifically expressed in different stages of PD by WGCNA, but validation by qRT-PCR showed inconsistent results; the remaining 5 miRNAs did not exhibit significant differences by qRT-PCR. ConclusionsThis study revealed that the 7 serum exosomal miRNAs (hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-199a-3p, hsa-miR-195-5p, hsa-miR-28-5p, hsa-miR-22-5p and hsa-miR-151a-5p) we screened out may potentially be used as biomarkers for progression and early grading diagnosis of PD in the population.

scholarly journals Transcriptome sequencing reveals a lncRNA–mRNA interaction network in extramammary Paget’s disease

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Da-chao Zheng ◽  
Yan-ting Shen ◽  
Zi-wei Wei ◽  
Xiang Wan ◽  
Min-kai Xie ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Paget’S Disease ◽  
Interaction Network ◽  
Paget's Disease ◽  
Differentially Expressed ◽  
Healthy Controls ◽  
Extramammary Paget’S Disease ◽  
Extramammary Paget's Disease

Abstract Background Extramammary Paget’s disease (EMPD) is a rare malignant intraepidermal adenocarcinoma that is poorly understood. Regulatory long noncoding RNAs (lncRNAs) are characterized in many species and shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in different diseases, especially in cancer studies. In the present study, we used high-throughput sequencing to reveal the lncRNA–mRNA interaction network in extramammary Paget’s disease. Methods High-throughput sequencing was used to identify differentially expressed lncRNA and mRNA profiles between EMPD patients and healthy controls. Then, a series of bioinformatics analyses were conducted to construct the lncRNA–mRNA interaction network, which was finally confirmed in vitro. Results Six pairs of EMPD tumor and normal skin samples were collected and sequenced to identify the differentially expressed lncRNA and mRNA profiles between EMPD and healthy controls. A total of 997 differentially expressed mRNAs and 785 differentially expressed lncRNAs were identified. The GO and KEGG analyses show that epidermal development and cell adhesion play important roles in EMPD. The results of the lncRNA–mRNA interaction network analysis suggested that NEAT1, PGAP1, FKBP5 and CDON were the pivotal nodes of the network and that lncRNA NEAT1 might regulate mRNA PGAP1, FKBP5 and CDON. The results of the quantitative real-time RT–PCR performed in ten other patients for NEAT1, PGAP1, FKBP5 and CDON were consistent with those of the sequencing analysis. Moreover, an in vitro experiment confirmed the interactions between NEAT1 and PGAP1, FKBP5 and CDON in human immortalized keratinocytes. Conclusion These findings suggest that the lncRNA–mRNA interaction network based on four pivotal nodes, NEAT1, PGAP1 FKBP5 and CDON, may play an important role in EMPD, which will contribute to a deeper understanding of the pathogenesis of EMPD.

scholarly journals Deregulation of lncRNA HIST1H2AG-6 and AIM1-3 in peripheral blood mononuclear cells is associated with newly diagnosed type 2 diabetes

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hui Jiang ◽  
Peian Lou ◽  
Xiaoluo Chen ◽  
Chenguang Wu ◽  
Shihe Shao
Keyword(s):  
Roc Curve ◽  
Multivariate Logistic Regression Analysis ◽  
Rank Correlation ◽  
Differentially Expressed ◽  
Healthy Controls ◽  
Biological Functions ◽  
Multivariate Logistic Regression ◽  
Spearman’S Rank Correlation ◽  
Spearman’S Rank Correlation Coefficient

Abstract Background Type 2 diabetes mellitus (T2DM) is mainly affected by genetic and environmental factors; however, the correlation of long noncoding RNAs (lncRNAs) with T2DM remains largely unknown. Methods Microarray analysis was performed to identify the differentially expressed lncRNAs and messenger RNAs (mRNAs) in patients with T2DM and healthy controls, and the expression of two candidate lncRNAs (lnc-HIST1H2AG-6 and lnc-AIM1-3) were further validated using quantitative real-time polymerase chain reaction (qRT-PCR). Spearman’s rank correlation coefficient was used to measure the degree of association between the two candidate lncRNAs and differentially expressed mRNAs. Furthermore, the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway and GO (Gene Ontology) enrichment analysis were used to reveal the biological functions of the two candidate lncRNAs. Additionally, multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed. Results The microarray analysis revealed that there were 55 lncRNAs and 36 mRNAs differentially expressed in patients with T2DM compared with healthy controls. Notably, lnc-HIST1H2AG-6 was significantly upregulated and lnc-AIM1-3 was significantly downregulated in patients with T2DM, which was validated in a large-scale qRT-PCR examination (90 controls and 100 patients with T2DM). Spearman’s rank correlation coefficient revealed that both lncRNAs were correlated with 36 differentially expressed mRNAs. Furthermore, functional enrichment (KEGG and GO) analysis demonstrated that the two lncRNA-related mRNAs might be involved in multiple biological functions, including cell programmed death, negative regulation of insulin receptor signal, and starch and sucrose metabolism. Multivariate logistic regression analysis revealed that lnc-HIST1H2AG-6 and lnc-AIM1-3 were significantly correlated with T2DM (OR = 5.791 and 0.071, respectively, both P = 0.000). Furthermore, the ROC curve showed that the expression of lnc-HIST1H2AG-6 and lnc-AIM1-3 might be used to differentiate patients with T2DM from healthy controls (area under the ROC curve = 0.664 and 0.769, respectively). Conclusion The profiles of lncRNA and mRNA were significantly changed in patients with T2DM. The expression levels of lnc-HIST1H2AG-6 and lnc-AIM1-3 genes were significantly correlated with some features of T2DM, which may be used to distinguish patients with T2DM from healthy controls and may serve as potential novel biomarkers for diagnosis in the future.

scholarly journals Peripheral Circulating Exosomal miRNAs Potentially Contribute to the Regulation of Molecular Signaling Networks in Aging

2020 ◽  
Vol 21 (6) ◽  
pp. 1908 ◽  
Author(s):  
Hongxia Zhang ◽  
Kunlin Jin
Keyword(s):  
Target Genes ◽  
Differentially Expressed ◽  
Molecular Signaling ◽  
Slow Development ◽  
Exosomal Mirnas ◽  
Pathways Analysis ◽  
Old Rats ◽  
Underlying Mechanisms ◽  
Signaling Components ◽  
Serum Exosomes

People are living longer than ever. Consequently, they have a greater chance for developing a functional impairment or aging-related disease, such as a neurodegenerative disease, later in life. Thus, it is important to identify and understand mechanisms underlying aging as well as the potential for rejuvenation. Therefore, we used next-generation sequencing to identify differentially expressed microRNAs (miRNAs) in serum exosomes isolated from young (three-month-old) and old (22-month-old) rats and then used bioinformatics to explore candidate genes and aging-related pathways. We identified 2844 mRNAs and 68 miRNAs that were differentially expressed with age. TargetScan revealed that 19 of these miRNAs are predicated to target the 766 mRNAs. Pathways analysis revealed signaling components targeted by these miRNAs: mTOR, AMPK, eNOS, IGF, PTEN, p53, integrins, and growth hormone. In addition, the most frequently predicted target genes regulated by these miRNAs were EIF4EBP1, insulin receptor, PDK1, PTEN, paxillin, and IGF-1 receptor. These signaling pathways and target genes may play critical roles in regulating aging and lifespan, thereby validating our analysis. Understanding the causes of aging and the underlying mechanisms may lead to interventions that could reverse certain aging processes and slow development of aging-related diseases.

scholarly journals Salivary Circular RNAs Hsa_Circ_0001874 and Hsa_Circ_0001971 as Novel Biomarkers for the Diagnosis of Oral Squamous Cell Carcinoma

2018 ◽  
Vol 47 (6) ◽  
pp. 2511-2521 ◽  
Author(s):  
Si-Yu Zhao ◽  
Jun Wang ◽  
Shao-Bo Ouyang ◽  
Zi-Kun Huang ◽  
Lan Liao
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Roc Curve ◽  
Tnm Stage ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Healthy Controls ◽  
Novel Biomarkers

Background/Aims: Recent studies have demonstrated that circular RNAs (circRNAs) can serve as potential molecular markers for disease diagnosis. However, little is known about their diagnostic potential for oral squamous cell carcinoma (OSCC). This study aimed to determine the expression of circRNAs in the saliva of OSCC patients to identify novel biomarkers for OSCC screening. Methods: Microarray screening of circRNA was performed to identify differentially expressed circRNAs in saliva from 3 OSCC patients compared with 3 healthy controls. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the results, and the association between these confirmed salivary circRNAs and clinicopathological features was analyzed using the chi-squared test. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of the circRNAs identified. Preoperative expression and postoperative expression (1 month after the surgery) of hsa_circ_0001874 and hsa_circ_0001971 was also determined. Results: Our results indicated 12 upregulated and 20 downregulated circRNAs in the saliva from the OSCC patients compared with that from the healthy controls. Among the differentially expressed circRNAs, hsa_circ_0001874, hsa_circ_0001971, and hsa_circ_0008068 were upregulated and hsa_circ_0000140, hsa_circ_0002632, and hsa_circ_0008792 were downregulated in the OSCC group versus the healthy group. Clinical data indicated that salivary hsa_circ_0001874 was correlated with TNM stage (P=0.006) and tumor grade (P=0.023) and that hsa_circ_0001971 was correlated with TNM stage (P=0.019). The combination of hsa_circ_0001874 and hsa_circ_0001971 showed an area under the ROC curve of 0.922 (95% confidence interval, 0.883-0.961; P< 0.001). The risk score based on the combination of hsa_circ_0001874 and hsa_circ_0001971 also discriminated patients with OSCC from patients with oral leukoplakia (P< 0.001). Moreover, the expression levels of salivary hsa_circ_0001874 and hsa_circ_0001971 were clearly decreased in the postoperative samples compared with preoperative samples (P< 0.001). Conclusions: This is the first study to demonstrate the potential of salivary hsa_circ_0001874 and hsa_circ_0001971 as biomarkers for the diagnosis of OSCC.

scholarly journals Identification of Exogenous Nitric Oxide-Responsive miRNAs from Alfalfa (Medicago sativa L.) under Drought Stress by High-Throughput Sequencing

Genes ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 30
Author(s):  
Yaodong Zhao ◽  
Wenjing Ma ◽  
Xiaohong Wei ◽  
Yu Long ◽  
Ying Zhao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Drought Stress ◽  
Medicago Sativa ◽  
High Throughput ◽  
Drought Resistance ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Medicago Sativa L

Alfalfa (Medicago sativa L.) is a high quality leguminous forage. Drought stress is one of the main factors that restrict the development of the alfalfa industry. High-throughput sequencing was used to analyze the microRNA (miRNA) profiles of alfalfa plants treated with CK (normal water), PEG (polyethylene glycol-6000; drought stress), and PEG + SNP (sodium nitroprusside; nitric oxide (NO) sprayed externally under drought stress). We identified 90 known miRNAs belonging to 46 families and predicted 177 new miRNAs. Real-time quantitative fluorescent PCR (qRT-PCR) was used to validate high-throughput expression analysis data. A total of 32 (14 known miRNAs and 18 new miRNAs) and 55 (24 known miRNAs and 31 new miRNAs) differentially expressed miRNAs were identified in PEG and PEG + SNP samples. This suggested that exogenous NO can induce more new miRNAs. The differentially expressed miRNA maturation sequences in the two treatment groups were targeted by 86 and 157 potential target genes, separately. The function of target genes was annotated by gene ontology (GO) enrichment and kyoto encyclopedia of genes and genomes (KEGG) analysis. The expression profiles of nine selected miRNAs and their target genes verified that their expression patterns were opposite. This study has documented that analysis of miRNA under PEG and PEG + SNP conditions provides important insights into the improvement of drought resistance of alfalfa by exogenous NO at the molecular level. This has important scientific value and practical significance for the improvement of plant drought resistance by exogenous NO.

scholarly journals Identification and study of differentially expressed miRNAs in aged NAFLD rats based on high-throughput sequencing

2020 ◽  
Vol 19 (3) ◽  
pp. 302-312 ◽  
Author(s):  
Ying Zhang ◽  
Danni Xiang ◽  
Xiaona Hu ◽  
Qingwei Ruan ◽  
Lina Wang ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas

Neurobehavioral Status and Health-Related Quality of Life in Newly Diagnosed High-Grade Glioma Patients

2001 ◽  
Vol 19 (20) ◽  
pp. 4037-4047 ◽  
Author(s):  
Martin Klein ◽  
Martin J.B . Taphoorn ◽  
Jan J. Heimans ◽  
Henk M. van der Ploeg ◽  
W. Peter Vandertop ◽  
...  
Keyword(s):  
High Grade Glioma ◽  
Extent Of Resection ◽  
High Grade ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
Health Related Quality ◽  
Related Quality ◽  
Health Related ◽  
Nsclc Patients

PURPOSE: To evaluate the health-related quality of life (HRQOL) and cognitive functioning of high-grade glioma patients in the postneurosurgical period. PATIENTS AND METHODS: The HRQOL, as assessed by the Short-Form Health Survey-36, tumor-specific symptoms, and objective and subjective neuropsychologic functioning, of 68 newly diagnosed glioma patients were compared with that of 50 patients with non–small-cell lung cancer (NSCLC) and to age- and sex-matched healthy controls. The association between tumor lateralization, extent of resection, and use of medication, and the HRQOL outcomes was also investigated. RESULTS: The HRQOL of the two patient groups was similar but significantly lower than that of the healthy controls. Glioma patients reported significantly more neurologic symptoms and poorer objective and subjective neuropsychologic functioning than the NSCLC patients. Using healthy controls as the reference group, cognitive impairment assessed at the individual patient level was observed in all glioma patients and 52% of the NSCLC patients. Poor performance on timed tasks in the glioma group could be attributed, in large part, to visual and motor deficits. Tumor lateralization was found to affect neuropsychologic functioning in a predictable manner. The extent of resection was not related significantly to neuropsychologic functioning. Corticosteroid use was associated with better recognition memory, whereas antiepileptic drug use was correlated negatively with working memory capacity. CONCLUSION: The general HRQOL of glioma patients is similar to that of patients with NSCLC. However, they suffer from a number of condition-specific neurologic and neuropsychologic problems that have a significant impact on their daily lives in the postsurgical period, before treatment with radiotherapy.

scholarly journals P17.74 * MONOFOCAL LESION OF DEMYELINATING DISEASE AND DIFFERENTIAL DIAGNOSIS WITH HIGH GRADE GLIOMA - CASE REPORT

2014 ◽  
Vol 16 (suppl 2) ◽  
pp. ii105-ii105
Author(s):  
F. Romeo ◽  
G. Maddalena ◽  
V. Conserva ◽  
V. Fumai ◽  
L. Fiorentino ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Case Report ◽  
Demyelinating Disease ◽  
High Grade Glioma ◽  
High Grade ◽  
Glioma Case
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