scholarly journals The diagnostic values of circulating miRNAs for hypertension and bioinformatics analysis

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Xiaoyi Zhang ◽  
Xiaoyan Wang ◽  
Jian Wu ◽  
Juan Peng ◽  
Xin Deng ◽  
...  

Few studies have compared the performances of those reported miRNAs as biomarkers for hypertension in a same cohort, we aimed to comprehensively examine the performances of those reported miRNAs as biomarkers for hypertension and identify the genes and pathways targetted by these miRNAs. Serum samples were collected from patients hospitalized for hypertension in Zhongshan Hospital. Gene expressions of 25 miRNAs were compared between hypertension and normal groups. Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of those miRNAs as biomarkers for hypertension. miRWALK2.0 and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to predict the target genes and pathways of selected miRNAs. A total of 164 participants were enrolled, amongst which 53 were patients with hypertension, 111 were normal population. MiR-122-5p (area under curve (AUC): 0.750), miR-199a-3p (AUC: 0.744), miR-208a-3p (AUC: 0.743), miR-423-5p (AUC: 0.740), and miR-223-5p (AUC: 0.718) showed better performance than others, and the best performance was the combination of miR-199a-3p, miR-208a-3p, miR-122-5p, and miR-223-3p (AUC: 0.80). Pathway analysis revealed that 94 pathways enriched with genes targetted by miR-199a-3p, miR-208a-3p, miR-122-5p, miR-223-5p. FoxO signaling was enriched with genes targetted by all the three miRNAs (miR-199a-3p, miR-208a-3p, miR-122-5p). The combination of miR-199a-3p, miR-208a-3p, miR-122-5p, and miR-223-3p has a good diagnostic performance for hypertension, and multitudes of possible mechanisms/pathways through which dysregulation of these miRNAs may impact risk of hypertension.

2020 ◽  
Author(s):  
Qiang Ma

Abstract Background: Primary central nervous system lymphoma (PCNSL), a rare form of the non-Hodgkin's lymphoma (NHL), usually has a poor prognosis, and molecular pathogenesis of PCNSL has not been fully elucidated. Here, potential miRNA biomarkers were investigated in patients with PCNSL using an integrated bioinformatics analysis. Methods: Expression profile arrays (GSE122011, GSE139031, and GSE25297) were obtained from the Gene Expression Omnibus (GEO). Free-scale miRNA co-expression networks were constructed with 27 PCNSL patients from GSE122011 by the weighted gene co-expression network analysis (WGCNA) in order to identify candidate biomarkers. Subsequently, miRNA-miRNA networks were visualized with the Cytoscape. Expression of candidate miRNAs was assessed in serum samples from GSE139031, including 42 PCNSL patients and 77 non-cancer individuals, and the sensitivity and the specificity were assessed by the receiver operating characteristic (ROC) curve. From GSE25297, differentially expressed genes (DEGs) from the PCNSL tissues (n = 7) and the normal lymph nodes (n = 7) were compared, target genes of candidate miRNAs were downloaded from TargetScan database, and target genes that were also down-regulated in GSE25297 were used to construct the protein-protein interaction (PPI) networks and for the gene ontology (GO) analysis. Results: miRNAs were clustered into two groups with 8 modules in 27 patients with PCNSL. One group consisted of the yellow and the turquoise modules, and the second group consisted of the other six modules. In the miRNA-miRNA network, the highest nodes were observed between miR-432 and miR-330-3p, which were from the yellow and the turquoise modules, and only miR-432 was closely associated with both the yellow (0.977, P = 2.88E -18 ) and the turquoise modules (0.525, P = 0.005). Additionally, patients with PCNSL had higher serum miR-432 expression compared with that in the non-cancer controls in GSE139031, and miR-432 has a higher accuracy for discriminating between PCNSL and non-cancer samples (AUC: 0.77; 95% CI: 0.6923 to 0.8550). For target genes of miR-432, RASGRF , DGKG , SMIM22 , SPOCD1 , NRCAM , CNTN2 , PTPRD , POTED , IGSF3 , SLC24A2 , CTNND2 , AIF1L , TMEM229A , GLDN , and MOBP were down-regulated in the PCNSL tissues. Among them, CTNND2 , GLDN , NRCAM , and PTPRD were associated with cell adhesion. Conclusion: Up-regulated miR-432 expression is a novel biomarker for patients with PCNSL and may be associated with cell adhesion.


2019 ◽  
Vol 14 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Jian Li ◽  
Sun Qiyu ◽  
Tiezheng Wang ◽  
Boxun Jin ◽  
Ning Li

AbstractEarly diagnosis of hepatocellular carcinoma (HCC) greatly improves the survival and prognosisfor patients. In this study weevaluate the diagnostic promise of combining serum alpha-fetoprotein (AFP) expression with two potential biomarkers, serum glypican-3 (GPC3) and expression of the micro-RNA miR-122 for hepatitis C virus (HCV) related early-stage HCC. For this study serum samples from 47 patients with early-stage HCC, 54 chronic HCV (CH) carriers, 35 patients with liver cirrhosis (LC) and 54 health controls (HC) were collected. In addition to routine laboratory investigations, serum AFP, GPC3 and miR-122 were measured in all patients and healthy controls. Receiver operating characteristic (ROC) curves were used to present sensitivity and specificity for the biomarkers. The three markers were all significantly elevated in the serum samples from HCC patients. ROC curves showed the three markers had similar diagnostic capacities for distinguishing early-stage HCC from HCV-positive controls (LC + CH). In order to distinguish early-stage HCC from high-risk LC patients, the expression of miR-122 was superior to GPC3. Combination of the three markers as a panel showed a better diagnostic performance than any of the single markers (P <0.05). Overall, this study revealed that serum expression of GPC3 and miR-122 may be useful biomarkers to combine with serum AFP expression for the diagnosis of HCV related early-stage HCC.


2017 ◽  
Vol 37 (1) ◽  
Author(s):  
Nian-sheng Lai ◽  
Jia-qi Zhang ◽  
Fei-yun Qin ◽  
Bin Sheng ◽  
Xing-gen Fang ◽  
...  

miRNAs are important regulators of translation and have been associated with the pathogenesis of a number of cardiovascular diseases including stroke and may be possible prognostic biomarkers. The purpose of the present study was to determine the expression levels of miRNAs in the sera of subarachnoid haemorrhage (SAH) patients and to evaluate their relationships with the severity and clinical outcome of SAH. Serum samples on day 3 after the onset of SAH were subjected to microarray analysis with Exqion miRCURYTM LNA array and quantitative PCR analysis. Serum samples from SAH patients (n=60) and healthy controls (n=10) were subjected to quantitative PCR analysis. The severities and clinical outcomes of the SAH patients were evaluated with the WFNS grade and the Modified Rankin Scale (mRS). Three miRNAs, miR-502-5p, miR-1297 and miR-4320 were significantly up-regulated in the sera of SAH patients when compared with the healthy controls. The serum miR-502-5p and miR-1297 levels were significantly higher in the patients with severe SAH and a poor outcome than in those with mild SAH and a good outcome (P<0.05). The areas under the receiver operating characteristic (ROC) curves (AUCs) of miR-502-5p, miR-1297 and miR-4320 to distinguish the SAH patients from the healthy controls were 0.958 (P<0.001), 0.950 (P<0.001) and 0.843 (P<0.001) respectively. Taken together, these results indicate that miR-502-5p and miR-1297 are potentially valuable indicators of the diagnosis, severity and prognosis of SAH, and miR-4320 was a potentially valuable indicator of the diagnosis of SAH.


2020 ◽  
Vol 18 ◽  
pp. 205873922096118
Author(s):  
Yan Qin ◽  
Yanyao Wu ◽  
Min Feng ◽  
Yanlin Wang ◽  
Xiangcong Zhao ◽  
...  

Detection of autoantibody against extractable nuclear antigens (ENAs) plays a critical role in the diagnosis and management of autoimmune diseases.In this study, we assessed the performance of LETIA in detecting anti-ENAs. Total 606 serum samples from the Second Hospital of Shanxi Medical University were collected. Anti-SSA, anti-SSB, anti-Sm, anti-U1-snRNP, and anti-Sm/RNP were parallelly detected by LETIA and line immunoblot (LIA). Besides, this study assessed LETIA for its repeatability in detecting anti-ENAs autoantibodies, and consistency with LIA. A receiver operating characteristic (ROC) curves was drawn to assess the accuracy of LETIA. The LETIA and LIA showed high coincidence rate in detecting anti-SSA, anti-SSB, anti-Sm, anti-U1-snRNP, and anti-Sm/RNP autoantibodies, with the results being 87.22%, 96.61%, 97.03%, 88.28%, and 92.06%, respectively. Almost perfect consistency (kappa > 0.8) were found in the detection of anti-SSB and anti-Sm by LETIA and LIA. While in the detection of anti-SSA, anti-U1-snRNP, and anti-Sm/RNP, moderate consistency (0.6 ⩽ kappa ⩽ 0.8) were shown. The AUCs of anti-SSA, anti-SSB, anti-Sm, anti-U1-snRNP, and anti-Sm/RNP detected by LETIA were 0.972 (95% confidence interval (CI): 0.941–1.000, p < 0.001), 0.986 (95% CI: 0.967–1.000, p < 0.001), 0.912 (95% CI: 0.763–1.000, p < 0.001), 0.829 (95% CI: 0.731–0.928, p < 0.001), and 0.828 (95% CI: 0.715–0.941, p < 0.001), respectively. LETIA and LIA showed considerable consistency in detecting anti-ENAs. Moreover, with the pronounced advantages of automatic and rapid detection, and high universality, LETIA can meet the requirements for quantitative detection of anti-ENAs.


2020 ◽  
Vol 16 ◽  
pp. 117693432092057
Author(s):  
Lijun Yu ◽  
Meiyan Wei ◽  
Fengyan Li

Despite advances in the treatment of cervical cancer (CC), the prognosis of patients with CC remains to be improved. This study aimed to explore candidate gene targets for CC. CC datasets were downloaded from the Gene Expression Omnibus database. Genes with similar expression trends in varying steps of CC development were clustered using Short Time-series Expression Miner (STEM) software. Gene functions were then analyzed using the Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Protein interactions among genes of interest were predicted, followed by drug-target genes and prognosis-associated genes. The expressions of the predicted genes were determined using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Red and green profiles with upward and downward gene expressions, respectively, were screened using STEM software. Genes with increased expression were significantly enriched in DNA replication, cell-cycle-related biological processes, and the p53 signaling pathway. Based on the predicted results of the Drug-Gene Interaction database, 17 drug-gene interaction pairs, including 3 red profile genes (TOP2A, RRM2, and POLA1) and 16 drugs, were obtained. The Cancer Genome Atlas data analysis showed that high POLA1 expression was significantly correlated with prolonged survival, indicating that POLA1 is protective against CC. RT-qPCR and Western blotting showed that the expressions of TOP2A, RRM2, and POLA1 gradually increased in the multistep process of CC. TOP2A, RRM2, and POLA1 may be targets for the treatment of CC. However, many studies are needed to validate our findings.


2022 ◽  
Author(s):  
Yanyang Chen ◽  
Huhu Wang ◽  
Xiyao Chen ◽  
Hairong Ma ◽  
Jingjie Zheng ◽  
...  

Abstract Background: Although many markers are used for diagnosis of periprosthetic joint infection (PJI), serological screening and diagnosis for PJI are still challenging. We evaluated the performance of serum D-lactate and compared it with ESR, coagulation-related biomarkers and synovial D-lactate for the diagnosis of PJI.Methods: Consecutive patients with preoperative blood and intraoperative joint aspiration of a prosthetic hip or knee joint before revision arthroplasty were prospectively included. The diagnosis of PJI was based on the criteria of the Musculoskeletal Infection Society, and the diagnostic values of markers were estimated based on receiver operating characteristic (ROC) curves by maximizing sensitivity and specificity using optimal cutoff values.Results: Of 52 patients, 26 (50%) were diagnosed with PJI, and 26 (50%) were diagnosed with aseptic failure. ROC curves showed that serum D-lactate, fibrinogen (FIB) and ESR had equal areas under the curve (AUCs) of 0.80, followed by D-dimer and fibrin degradation product, which had AUCs of 0.67 and 0.69, respectively. Serum D-lactate had the highest sensitivity of 88.46% at the optimal threshold of 1.14 mmol/L, followed by FIB and ESR, with sensitivities of 80.77% and 73.08%, respectively, while there were no significant differences in specificity (73.08%, 73.08% and 76.92%, respectively). Conclusion: Serum D-lactate showed similar performance to FIB and ESR for diagnosis of PJI. The advantages of serum D-lactate are pathogen-specific, highly sensitive, minimally invasive and rapidly available making serum D-lactate useful as a point-of-care screening test for PJI.


2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Jiaming Yao ◽  
Junbin Yan ◽  
Jinting Wu ◽  
Jianshun Yu ◽  
Beihui He ◽  
...  

Background. San-Huang-Chai-Zhu formula (SHCZF) has been used to improve cholestasis for many years. This study aims to predict the possible gene targets of SHCZF in treating acute intrahepatic cholestasis (AIC) in rats. Materials and Methods. Eighteen SD rats were randomly assigned to the normal group, ANIT group, and ANIT + SHCZF group. Alpha-naphthylisothiocyanate (ANIT) was used to induce AIC. Serum biochemical indexes were detected in each group. After treatment, the livers were collected and used to extract RNA. The library was constructed by TruSeq RNA, sequenced by Illumina, and analyzed by various bioinformatics methods. qRT-PCR was used to verify the target genes related to the efficacy of SHCZF. Results. Serum ALT, AST, ALP, and TBIL were significantly higher in the ANIT group than in the normal group. Serum ALT and AST levels in the ANIT + SHCZF group were substantially lower than those in the ANIT group. A total of 354 intersected genes were screened by expression level correlation and PCA analysis, GO and KEGG pathway enrichment analysis, and WGCNA and STEM analysis. Then, 4 overlapping genes were found by pathway/BP/gene network construction. SHCZF reversed the downregulation of expression of CYP4A1 and HACL1 and the upregulation of expression of DBI and F11R induced by ANIT. In addition, the qRT-PCR result showed that mRNA expression of CYP4A1, HACL1, and F11R genes in the liver was consistent with the prediction result of bioinformatics analysis. Conclusion. CYP4A1, HACL1, and F11R are genes related to the occurrence of ANIT-induced AIC in rats and may be considered as targets of SHCZF for the treatment of AIC.


Epigenomics ◽  
2021 ◽  
Author(s):  
Yanlin Feng ◽  
Souraka Tapara Dramani Maman ◽  
Xinyu Zhu ◽  
Xuefang Liu ◽  
Christian Cedric Bongolo ◽  
...  

This study aimed to unveil the functional roles of LINC00221 in hepatocellular carcinoma (HCC). A discovery cohort and a validation cohort were respectively used to identify and verify the clinical value of LINC00221 in HCC. Bioinformatics analysis was performed to explore its potential mechanisms. LINC00221 was upregulated in HCC tissues and serum samples. Survival analysis and receiver operating characteristic curve further revealed its prognostic and diagnostic roles. Exploration of the mechanism showed that LINC00221 might exert a pro-cancer role via the lncRNA–miRNA–mRNA network. Our study reveals that upregulated LINC00221 can serve as a potential diagnostic and prognostic biomarker and provides novel clues as to the role of LINC00221 in HCC.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu Zhou ◽  
Yuqing Wang ◽  
Mingying Lin ◽  
Daiqian Wu ◽  
Min Zhao

Abstract Background Cervical cancer (CC) is one of the most common gynaecological malignancies all around the world. The mechanisms of cervical carcinoma formation remain under close scrutiny. The long non-coding RNAs (lncRNA) and microRNAs (miRNAs) play important roles in controlling gene expression and promoting the development and progression of cervical cancer by acting as competitive endogenous RNA (ceRNA). However, the roles of lncRNA associated with ceRNAs in cervical carcinogenesis remains unknown. In this study, the expression of long non-coding RNA HOTAIR was investigated in HPV16 positive cervical cancer cells, the candidate miRNAs and target genes were identified to clarify putative ceRNAs of HOTAIR/miRNA in cervical cancer cells. Methods The proliferation ability of cells was measured by CCK8 and EdU incorporation assays and cell apoptosis was analyzed by flow cytometry. The expression of HOTAIR, miR-214-3p, HPV16 E7 mRNA were detected by qRT-PCR. As for searching for the interaction between miR-214-3p and HOTAIR, the binding sites for miR-214-3p on HOTAIR was predicted by starbase v2.0 database, then dual-luciferase assay was used to verify the binding sites. In addition, Gene Ontology (GO) and protein–protein interaction (PPI) network analysis of target genes of miR-214-3p were performed with bioinformatics analysis. The potential signal pathway regulated by HOTAIR/miR-214-3p was predicted by KEGG enrichment analysis and confirmed by qPCR and WB analysis in cervical cancer cells. Results Our results showed that expression of HOTAIR was up-regulated, while that of miR-214-3p was down-regulated in HPV16-positive cervical cancer cells. The expression status of HPV16 E7 played an important role in regulating expression of HOTAIR or miR-214-3p in cervical cancer cells. HOTAIR knockdown could significantly inhibited cell proliferate ability and promote cellular apoptosis, whereas the inhibition of miR-214-3p expression partially reversed such results. Bioinformatics analysis identified 1451 genes as target genes of miR-214-3p. The Gene ontology (GO) and KEGG Pathway enrichment analysis showed that these target genes were mainly related to regulation of cell communication, protein binding, enzyme binding and transferase activity, and Wnt ligand biogenesis. Pathway enrichment analysis results showed that the predicted target genes were significantly enriched in Wnt/β-catenin signaling pathway. Finally, our results confirmed that miR-214-3p could significantly inhibit β-catenin expression in HPV16 positive cancer cells by qPCR and WB analysis. Conclusion HOTAIR could act as a ceRNA through binding to miR-214-3p, promote cell proliferation and inhibit the apoptosis of HPV16 positive cervical cancer. HOTAIR/miR-214-3p/Wnt/β-catenin signal pathway might played important regulated roles in HPV16 positive cervical cancer. Our results provided new insight into defining novel biomarkers for cervical cancer.


2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 241-241
Author(s):  
Keelee J McCarty ◽  
Andrea DeCarlo ◽  
Ralph Ricks ◽  
Scott Pratt ◽  
Nathan Long

Abstract The objective of this study was to determine the effects of maternal nutrient restriction during gestation on microRNA abundance in bovine serum. Primiparous Angus-cross cows (n = 22) were fed either control (CON; to gain 1 kg/wk) or nutrient restricted (NR; 0.55 % NEm) diets based on National Research Council requirements. On d 30 of gestation, cows were blocked by body condition and randomly assigned to one of three diets: CON fed from d 30 to 190 (n = 8), or NR/C (n = 7) or C/NR (n = 7) fed either the CON or NR diet from d 30 to 110 followed by CON or NR from d 110 to 190 of gestation. Maternal blood samples were collected the day before harvest on 190 d of gestation. RNA was isolated from serum samples using the mirVANA microRNA Isolation kit and analyzed using a previously validated miRNA microarray of known Bos Taurus sequences. MicroRNA abundance were analyzed via ANOVA using procedures correcting for false discovery rate of the microarray data. At d 190 of gestation, 26 miRNAs observed differential (P &lt; 0.05) abundance between treatments, in which 11 miRNAs were downregulated and 15 miRNAs were upregulated in both NR/CON and CON/NR compared to CON cows. Additionally, a set of miRNAs (bta-miR-2487_L-2R-3_1ss15CT, bta-miR-215, and bta-miR-760-5p) were differentially abundant (P &lt; 0.04) between NR/CON and CON/NR cows. Top KEGG pathway enrichment analysis of target genes included pathways in cancer, cAMP signaling pathway, axon guidance, long term potentiation, and insulin signaling. In summary, maternal nutrient restriction observed altered miRNA abundance irrespective of the time at which the nutritional insult was induced.


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