Dataset Information

Identification of potential prognostic ceRNA module biomarkers in patients with pancreatic adenocarcinoma.

ABSTRACT: Accumulating evidence suggested that long non-coding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs) to interact with other RNA transcripts and ceRNAs perturbation play important roles in cancer initiation and progression including pancreatic adenocarcinoma (PAAD). In this study, we constructed a PAAD-specific hallmark gene-related ceRNA network (HceNet) using paired genome-wide expression profiles of mRNA, lncRNA and miRNA and regulatory relationships between them. Based on "ceRNA hypothesis", we analyzed the characteristics of HceNet and identified a ceRNA module comprising of 29 genes (12 lncRNAs, two miRNAs and 15 mRNAs) as potential prognostic biomarkers related to overall survival of patients with PAAD. The prognostic value of ceRNA module biomarkers was further validated in the train (Hazard Ratio (HR) =1.661, 95% CI: 1.275-2.165, p<1.00e-4), test (HR=1.546, 95% CI: 1.238-1.930, p<1.00e-4), and entire (HR=1.559, 95% CI: 1.321-1.839, p<1.00e-4) datasets. Our study provides candidate prognostic biomarkers for PAAD and increases our understanding of ceRNA-related regulatory mechanism in PAAD pathogenesis.

SUBMITTER: Zhao L

PROVIDER: S-EPMC5706890 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Identification of potential prognostic ceRNA module biomarkers in patients with pancreatic adenocarcinoma.

Zhao Lili L Liu Bingrong B

Oncotarget 20171010 55

Accumulating evidence suggested that long non-coding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs) to interact with other RNA transcripts and ceRNAs perturbation play important roles in cancer initiation and progression including pancreatic adenocarcinoma (PAAD). In this study, we constructed a PAAD-specific hallmark gene-related ceRNA network (HceNet) using paired genome-wide expression profiles of mRNA, lncRNA and miRNA and regulatory relationships between them. Based on "c ...[more]

PMID: 29212244

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Project description:BackgroundMore and more studies have proven that circular RNAs (circRNAs) play vital roles in cancer development via sponging miRNAs. However, the expression pattern of competing endogenous RNA (ceRNA) in lung adenocarcinoma (LUAD) remains largely unclear. The current study explored functional roles and the regulatory mechanisms of circRNA as ceRNAs in LUAD and their potential impact on LUAD patient prognosis.MethodsIn this study, we systematically screened differential expression circRNAs (DEcircRNAs), miRNAs (DEmiRNAs) and mRNAs (DEGs) associated with LUAD. Then, DEcircRNAs, DEmiRNAs and DEGs were selected to construct a circRNA-miRNA-mRNA prognosis-related regulatory network based on interaction information from the ENCORI database. Subsequently, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the genes in the network to predict the potential underlying mechanisms and functions of circRNAs in LUAD. In addition, Kaplan-Meier survival analysis was performed to evaluate clinical outcomes of LUAD patients, and drug sensitivity analysis was used to screen potential biomarkers for drug treatment of patients with LUAD.ResultsAs a result, 10 circRNAs were aberrantly expressed in LUAD tissues. The ceRNA network was built, which included 3 DEcircRNAs, 6 DEmiRNAs and 157 DEGs. The DEGs in the ceRNA network of hsa_circ_0049271 enriched in biological processes of cell proliferation and the Jak-STAT signaling pathway. We also detected 7 mRNAs in the ceRNA network of hsa_circ_0049271 that were significantly associated with the overall survival of LUAD patients (P < 0.05). Importantly, four genes (PDGFB, CCND2, CTF1, IL7R) identified were strongly associated with STAT3 activation and drugs sensitivity in GDSC.ConclusionsIn summary, a ceRNA network of hsa_circ_0049271 was successfully constructed, which including one circRNA, two miRNAs, and seven mRNAs. Seven mRNAs (PDGFB, TNFRSF19, CCND2, CTF1, IL11RA, IL7R and MAOA) were remarkably associated with the prognosis of LUAD patients. Among seven mRNA species, four genes (PDGFB, CCND2, CTF1, and IL7R) could be considered as drug targets in LUAD. Our research will provide new insights into the prognosis-related ceRNA network in LUAD.

Project description:BackgroundCompeting endogenous RNAs (ceRNAs) are a newly identified type of regulatory RNA. Accumulating evidence suggests that ceRNAs play an important role in the pathogenesis of diseases such as cancer. Thus, ceRNA dysregulation may represent an important molecular mechanism underlying cancer progression and poor prognosis. In this study, we aimed to identify ceRNAs that may serve as potential biomarkers for early diagnosis of lung adenocarcinoma (LUAD).MethodsWe performed differential gene expression analysis on TCGA-LUAD datasets to identify differentially expressed (DE) mRNAs, lncRNAs, and miRNAs at different tumor stages. Based on the ceRNA hypothesis and considering the synergistic or feedback regulation of ceRNAs, a lncRNA-miRNA-mRNA network was constructed. Functional analysis was performed using gene ontology term and KEGG pathway enrichment analysis and KOBAS 2.0 software. Transcription factor (TF) analysis was carried out to identify direct targets of the TFs associated with LUAD prognosis. Identified DE genes were validated using gene expression omnibus (GEO) datasets.ResultsBased on analysis of TCGA-LUAD datasets, we obtained 2,610 DE mRNAs, 915 lncRNAs, and 125 miRNAs that were common to different tumor stages (|log2(Fold change)| ≥ 1, false discovery rate < 0.01), respectively. Functional analysis showed that the aberrantly expressed mRNAs were closely related to tumor development. Survival analyses of the constructed ceRNA network modules demonstrated that five of them exhibit prognostic significance. The five ceRNA interaction modules contained one lncRNA (FENDRR), three mRNAs (EPAS1, FOXF1, and EDNRB), and four miRNAs (hsa-miR-148a, hsa-miR-195, hsa-miR-196b, and hsa-miR-301b). The aberrant expression of one lncRNA and three mRNAs was verified in the LUAD GEO dataset. Transcription factor analysis demonstrated that EPAS1 directly targeted 13 DE mRNAs.ConclusionOur observations indicate that lncRNA-related ceRNAs and TFs play an important role in LUAD. The present study provides novel insights into the molecular mechanisms underlying LUAD pathogenesis. Furthermore, our study facilitates the identification of potential biomarkers for the early diagnosis and prognosis of LUAD and therapeutic targets for its treatment.

Dataset Information

Identification of potential prognostic ceRNA module biomarkers in patients with pancreatic adenocarcinoma.

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Identification of potential prognostic ceRNA module biomarkers in patients with pancreatic adenocarcinoma.

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