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LncRNA-mRNA co-expression analysis discovered the diagnostic and prognostic biomarkers and potential therapeutic agents for myocardial infarction.

ABSTRACT: Currently, the role of lncRNA in myocardial infarction (MI) is poorly understood. 17 co-expression modules were determined, specifically, the greenyellow, saddlebrown, grey60, royalblue, lightgreen, white, and pink modules were specifically expressed in the acute phase of MI, and brown, darkred, and royalblue, while greenyellow modules were specifically expressed in MI compared with CAD. 12 time-dependent of lncRNA/mRNA clusters with consistent expression trends were also identified. MI-associated modules were mainly enriched to immune, cell cycle, and metabolic pathways. We further obtained a network of 1816 lncRNA-mRNAs with higher expression correlations among these lncRNAs by analyzing the topological properties of the network. Herein, lncRNA RP11-847H18.2 and KLHL28, SPRTN, and EPM2AIP1 were determined as gene markers specifically expressed in MI, and they demonstrated a high predictive performance for MI diagnosis and prognosis. Three drugs, namely, Calcium citrate, Calcium Phosphate, and Calcium phosphate dihydrate, were identified as potential precursors of MI. Finally, gene and lncRNA diagnostic models were developed based on these genes and lncRNAs, with their AUCs averaged above 0.89 in both training and validation datasets. The findings of this study improve the diagnosis and prognosis of MI and personalized treatment of MI.

SUBMITTER: Zhang X

PROVIDER: S-EPMC8034908 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Cardiovascular magnetic resonance imaging is considered the reference methodology for cardiac morphology and function but requires manual postprocessing. Whether novel artificial intelligence-based automated analyses deliver similar information for risk stratification is unknown. Therefore, this study aimed to investigate feasibility and prognostic implications of artificial intelligence-based, commercially available software analyses. Methods and Results Cardiovascular magnetic resonance data (n=1017 patients) from 2 myocardial infarction multicenter trials were included. Analyses of biventricular parameters including ejection fraction (EF) were manually and automatically assessed using conventional and artificial intelligence-based software. Obtained parameters entered regression analyses for prediction of major adverse cardiac events, defined as death, reinfarction, or congestive heart failure, within 1 year after the acute event. Both manual and uncorrected automated volumetric assessments showed similar impact on outcome in univariate analyses (left ventricular EF, manual: hazard ratio [HR], 0.93 [95% CI 0.91-0.95]; P<0.001; automated: HR, 0.94 [95% CI, 0.92-0.96]; P<0.001) and multivariable analyses (left ventricular EF, manual: HR, 0.95 [95% CI, 0.92-0.98]; P=0.001; automated: HR, 0.95 [95% CI, 0.92-0.98]; P=0.001). Manual correction of the automated contours did not lead to improved risk prediction (left ventricular EF, area under the curve: 0.67 automated versus 0.68 automated corrected; P=0.49). There was acceptable agreement (left ventricular EF: bias, 2.6%; 95% limits of agreement, -9.1% to 14.2%; intraclass correlation coefficient, 0.88 [95% CI, 0.77-0.93]) of manual and automated volumetric assessments. Conclusions User-independent volumetric analyses performed by fully automated software are feasible, and results are equally predictive of major adverse cardiac events compared with conventional analyses in patients following myocardial infarction. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00712101 and NCT01612312.

Project description:Acute myocardial infarction (AMI) is a common cause of death in numerous countries. Understanding the molecular mechanisms of the disease and analyzing potential biomarkers of AMI is crucial. However, specific diagnostic biomarkers have thus far not been fully established and candidate regulatory targets for AMI remain to be determined. In the present study, the AMI gene chip dataset GSE48060 comprising blood samples from control subjects with normal cardiac function (n=21) and patients with AMI (n=26) was downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) between the AMI and control groups were identified with the online tool GEO2R. The co-expression network of DEGs was analyzed by calculating the Pearson correlation coefficient of all gene pairs, mutual rank screening and cutoff threshold screening. Subsequently, the Gene Ontology (GO) database was used to analyze the genes' functions and pathway enrichment of genes in the most important modules was performed. Kyoto Encyclopedia of Genes and Genomes (KEGG) Disease and BioCyc were used to analyze the hub genes in the module to determine important sub-pathways. In addition, the expression of hub genes was confirmed by reverse transcription-quantitative PCR in AMI and control specimens. In the present study, 52 DEGs, including 26 upregulated and 26 downregulated genes, were identified. As key hub genes, three upregulated genes (AKR1C3, RPS24 and P2RY12) and three downregulated genes (ACSL1, B3GNT5 and MGAM) were identified from the co-expression network. Furthermore, GO enrichment analysis of all AMI co-expression network genes revealed functional enrichment mainly in 'RAGE receptor binding' and 'negative regulation of T cell cytokine production'. In addition, KEGG Disease and BioCyc analysis indicated functional enrichment of the genes RPS24 and P2RY12 in 'cardiovascular diseases', of AKR1C3 in 'cardenolide biosynthesis', of MGAM in 'glycogenolysis', of B3GNT5 in 'glycosphingolipid biosynthesis' and of ACSL1 in 'icosapentaenoate biosynthesis II'. In conclusion, the hub genes AKR1C3, RPS24, P2RY12, ACSL1, B3GNT5 and MGAM are potential markers of AMI, and have potential application value in the diagnosis of AMI.

Project description:BackgroundThis study aims to reveal early breast cancer (BC) specific competing endogenous RNA (ceRNA) network through the expression profiles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and mRNAs.MethodsBased on The Cancer Genome Atlas (TCGA), we obtained the differentially expressed mRNAs, miRNAs, and lncRNAs (DEmRNAs, DEmiRNAs and DElncRNAs) between early BC and normal samples. The lncRNA-miRNA-mRNA interaction network was constructed using Cytoscape. Functional enrichment were performed using GeneCoDis3. The expression of selected genes were validated by qRT-PCR. Based on the published dataset, we validated the result of TCGA integration analysis. The diagnostic and prognostic value of candidate genes was evaluated by ROC curve analysis and survival analysis, respectively.ResultsTotally, 1207 DEmRNAs, 194 DElncRNAs and 37 DEmiRNAs were obtained. Functional enrichment analysis results showed that all of DEmRNAs were enriched in pathway of cytokine-cytokine receptor interaction, PPAR signaling pathway and pathways in cancer. The DEmRNA-DEmiRNA-DElncRNA interaction network in early BC was consisted of 23 DEmiRNAs, 95 DElncRNAs and 309 DEmRNAs. Among ceRNA network, IL-6-hsa-miR-182-5p-ADAMTS9-AS1 interactions, LIFR-hsa-miR-21-5p-ADAMTS9-AS1 interactions and MMP1/MMP11-hsa-miR-145-5p-CDKN2B-AS1 interactions were speculated to involve in the development of early BC. The qRT-PCR results were consistent with our integrated analysis. Except for ADAMTS9-AS1 and CDKN2B-AS1, expression of the others results in the Gene Expression Omnibus (GEO) dataset were generally consistent with TCGA integrated analysis. The area under curve (AUC) of the ADAMTS9-AS1, CDKN2B-AS1, IL-6, MMP11, hsa-miR-145-5p and hsa-miR-182-5p were 0.947, 0.862, 0.842, 0.993, 0.960 and 0.944, and the specificity and sensitivity of the 6 biomarkers were 83.4% and 95.6%, 72.2% and 90.3%, 80.1% and 74.3%, 96.2% and 96.5%, 90.1% and 92.3%, and 88.7% and 90.4%, respectively. In addition, IL-6 had potential prognostic value for early BC.ConclusionThese findings may provide novel insights into the lncRNA-miRNA-mRNA network and uncover potential therapeutic targets in early BC.

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LncRNA-mRNA co-expression analysis discovered the diagnostic and prognostic biomarkers and potential therapeutic agents for myocardial infarction.

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