A Competing Endogenous RNA Network Reveals Novel lncRNA, miRNA and mRNA Biomarkers With Diagnostic and Prognostic Value for Early Breast Cancer

Background: This 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. Methods: Based on The Cancer Genome Atlas (TCGA), we obtained the differentially expressed...

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Main Authors: Zhong-Bing Luo, Gui-E Lai MS, Tao Jiang MS, Chuan-Lin Cao MS, Tao Peng BS, Feng-En Liu BS
Format: Article
Language:English
Published: SAGE Publishing 2020-12-01
Series:Technology in Cancer Research & Treatment
Online Access:https://doi.org/10.1177/1533033820983293
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author Zhong-Bing Luo
Gui-E Lai MS
Tao Jiang MS
Chuan-Lin Cao MS
Tao Peng BS
Feng-En Liu BS
author_facet Zhong-Bing Luo
Gui-E Lai MS
Tao Jiang MS
Chuan-Lin Cao MS
Tao Peng BS
Feng-En Liu BS
author_sort Zhong-Bing Luo
collection DOAJ
description Background: This 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. Methods: Based 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. Results: Totally, 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. Conclusion: These findings may provide novel insights into the lncRNA-miRNA-mRNA network and uncover potential therapeutic targets in early BC.
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spelling doaj.art-f312079a4a4041c2a6d5305e959b5eb62022-12-21T17:25:53ZengSAGE PublishingTechnology in Cancer Research & Treatment1533-03382020-12-011910.1177/1533033820983293A Competing Endogenous RNA Network Reveals Novel lncRNA, miRNA and mRNA Biomarkers With Diagnostic and Prognostic Value for Early Breast CancerZhong-Bing Luo0Gui-E Lai MS1Tao Jiang MS2Chuan-Lin Cao MS3Tao Peng BS4Feng-En Liu BS5 Department of Breast Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou of Jiangxi Province, China Department of Breast Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou of Jiangxi Province, China Department of Breast Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou of Jiangxi Province, China Department of Breast Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou of Jiangxi Province, China Department of Breast Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou of Jiangxi Province, China Department of Breast Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou of Jiangxi Province, ChinaBackground: This 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. Methods: Based 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. Results: Totally, 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. Conclusion: These findings may provide novel insights into the lncRNA-miRNA-mRNA network and uncover potential therapeutic targets in early BC.https://doi.org/10.1177/1533033820983293
spellingShingle Zhong-Bing Luo
Gui-E Lai MS
Tao Jiang MS
Chuan-Lin Cao MS
Tao Peng BS
Feng-En Liu BS
A Competing Endogenous RNA Network Reveals Novel lncRNA, miRNA and mRNA Biomarkers With Diagnostic and Prognostic Value for Early Breast Cancer
Technology in Cancer Research & Treatment
title A Competing Endogenous RNA Network Reveals Novel lncRNA, miRNA and mRNA Biomarkers With Diagnostic and Prognostic Value for Early Breast Cancer
title_full A Competing Endogenous RNA Network Reveals Novel lncRNA, miRNA and mRNA Biomarkers With Diagnostic and Prognostic Value for Early Breast Cancer
title_fullStr A Competing Endogenous RNA Network Reveals Novel lncRNA, miRNA and mRNA Biomarkers With Diagnostic and Prognostic Value for Early Breast Cancer
title_full_unstemmed A Competing Endogenous RNA Network Reveals Novel lncRNA, miRNA and mRNA Biomarkers With Diagnostic and Prognostic Value for Early Breast Cancer
title_short A Competing Endogenous RNA Network Reveals Novel lncRNA, miRNA and mRNA Biomarkers With Diagnostic and Prognostic Value for Early Breast Cancer
title_sort competing endogenous rna network reveals novel lncrna mirna and mrna biomarkers with diagnostic and prognostic value for early breast cancer
url https://doi.org/10.1177/1533033820983293
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