Dataset Information

A seven-miRNA expression-based prognostic signature and its corresponding potential competing endogenous RNA network in early pancreatic cancer.

ABSTRACT: The present study aimed to establish a microRNA (miRNA/miR) signature to predict the prognosis of patients with pancreatic cancer (PC) at the early stage and to investigate the involvement of competing endogenous RNAs (ceRNAs) in PC. Using mature miRNA expression profiles from The Cancer Genome Atlas, differentially expressed miRNAs in tissues derived from patients exhibiting early PC and tissues from healthy individuals were compared. The least absolute shrinkage and selection operator regression method was used to construct a miRNA-based signature for predicting prognosis. The miRNet tool, gene set enrichment analysis (GSEA) and the LncRNADisease database were utilized to explore the mechanistic involvement of ceRNAs. A total of seven downregulated miRNAs in PC (miR-424-5p, miR-139-5p, miR-5586-5p, miR-126-3p, miR-3613-5p, miR-454-3p and miR-1271-5p) were selected to generate a signature. Based on this seven-miRNA signature, it was possible to stratify patients with PC into low- and high-risk groups. The overall survival of the low-risk group was significantly longer than that of the high-risk group (P<0.001). The seven-miRNA signature was able to predict the 2-year-survival rate of patients with early PC with an area under the curve of 0.750. Furthermore, as opposed to routine clinicopathological features, this seven-miRNA signature was an independent prognostic factor according to multivariate Cox regression analysis. GSEA indicated that the extracellular matrix receptor interaction pathway and the transforming growth factor-? signaling pathway were enriched in the high-risk group. A ceRNA network of the seven-miR signature was constructed. In conclusion, the present study provided a seven-miRNA signature, according to which patients with early PC may be divided into high- and low-risk groups. The ceRNA network of the prognostic signature was preliminarily explored.

SUBMITTER: Bai X

PROVIDER: S-EPMC6676175 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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A seven-miRNA expression-based prognostic signature and its corresponding potential competing endogenous RNA network in early pancreatic cancer.

Bai Xue X Lu Donglan D Lin Yan Y Lv Yufeng Y He Liusheng L

Experimental and therapeutic medicine 20190703 3

The present study aimed to establish a microRNA (miRNA/miR) signature to predict the prognosis of patients with pancreatic cancer (PC) at the early stage and to investigate the involvement of competing endogenous RNAs (ceRNAs) in PC. Using mature miRNA expression profiles from The Cancer Genome Atlas, differentially expressed miRNAs in tissues derived from patients exhibiting early PC and tissues from healthy individuals were compared. The least absolute shrinkage and selection operator regressi ...[more]

PMID: 31410115

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Project description:BackgroundIncreasing evidence has underscored the role of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in the development and progression of tumors. Nevertheless, lncRNA biomarkers in lncRNA-related ceRNA network that can predict the prognosis of breast cancer (BC) are still lacking. The aim of our study was to identify potential lncRNA signatures capable of predicting overall survival (OS) of BC patients.MethodsThe RNA sequencing data and clinical characteristics of BC patients were obtained from the Cancer Genome Atlas database, and differentially expressed lncRNA (DElncRNAs), DEmRNAs, and DEmiRNAs were then identified between BC and normal breast tissue samples. Subsequently, the lncRNA-miRNA-mRNA ceRNA network of BC was established, and the gene oncology enrichment analyses for the DEmRNAs interacting with lncRNAs in the ceRNA network was implemented. Using univariate and multivariate Cox regression analyses, a four-lncRNA signature was developed and used for predicting the survival in BC patients. We applied receiver operating characteristic analysis to assess the performance of our model.ResultsA total of 1061 DElncRNAs, 2150 DEmRNAs, and 82 DEmiRNAs were identified between BC and normal breast tissue samples. A lncRNA-miRNA-mRNA ceRNA network of BC was established, which comprised of 8 DEmiRNAs, 48 DElncRNAs, and 10 DEmRNAs. Further gene oncology enrichment analyses revealed that the DEmRNAs interacting with lncRNAs in the ceRNA network participated in cell leading edge, protease binding, alpha-catenin binding, gamma-catenin binding, and adenylate cyclase binding. A univariate regression analysis of the DElncRNAs revealed 7 lncRNAs (ADAMTS9-AS1, AC061992.1, LINC00536, HOTAIR, AL391421.1, TLR8-AS1 and LINC00491) that were associated with OS of BC patients. A multivariate Cox regression analysis demonstrated that 4 of those lncRNAs (ADAMTS9-AS1, LINC00536, AL391421.1 and LINC00491) had significant prognostic value, and their cumulative risk score indicated that this 4-lncRNA signature independently predicted OS in BC patients. Furthermore, the area under the curve of the 4-lncRNA signature associated with 3-year survival was 0.696.ConclusionsThe current study provides novel insights into the lncRNA-related ceRNA network in BC and the 4 lncRNA biomarkers may be independent prognostic signatures in predicting the survival of BC patients.

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.

Dataset Information

A seven-miRNA expression-based prognostic signature and its corresponding potential competing endogenous RNA network in early pancreatic cancer.

Publications

A seven-miRNA expression-based prognostic signature and its corresponding potential competing endogenous RNA network in early pancreatic cancer.

Similar Datasets

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