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Systematic analysis identifies three-lncRNA signature as a potentially prognostic biomarker for lung squamous cell carcinoma using bioinformatics strategy.

ABSTRACT: Background:Lung squamous cell carcinoma (LUSC) is the second most common histological subtype of lung cancer (LC), and the prognoses of most LUSC patients are so far still very poor. The present study aimed at integrating lncRNA, miRNA and mRNA expression data to identify lncRNA signature in competitive endogenous RNA (ceRNA) network as a potentially prognostic biomarker for LUSC patients. Methods:Gene expression data and clinical characteristics of LUSC patients were retrieved from The Cancer Genome Atlas (TCGA) database, and were integratedly analyzed using bioinformatics methods including Differentially Expressed Gene Analysis (DEGA), Weighted Gene Co-expression Network Analysis (WGCNA), Protein and Protein Interaction (PPI) network analysis and ceRNA network construction. Subsequently, univariate and multivariate Cox regression analyses of differentially expressed lncRNAs (DElncRNAs) in ceRNA network were performed to predict the overall survival (OS) in LUSC patients. Receiver operating characteristic (ROC) analysis was used to evaluate the performance of multivariate Cox regression model. Gene expression profiling interactive analysis (GEPIA) was used to validate key genes. Results:WGCNA showed that turquoise module including 1,694 DElncRNAs, 2,654 DEmRNAs as well as 113 DEmiRNAs was identified as the most significant modules (cor=0.99, P<1e-200), and differentially expressed RNAs in the module were used to subsequently analyze. PPI network analysis identified FPR2, GNG11 and ADCY4 as critical genes in LUSC, and survival analysis revealed that low mRNA expression of FPR2 and GNG11 resulted in a higher OS rate of LUSC patients. A lncRNA-miRNA-mRNA ceRNA network including 121 DElncRNAs, 18 DEmiRNAs and 3 DEmRNAs was established, and univariate and multivariate Cox regression analysis of those 121 DElncRNAs showed a group of 3 DElncRNAs (TTTY16, POU6F2-AS2 and CACNA2D3-AS1) had significantly prognostic value in OS of LUSC patients. ROC analysis showed that the area under the curve (AUC) of the 3-lncRNA signature associated with 3-year survival was 0.629. Conclusions:The current study provides novel insights into the lncRNA-related regulatory mechanisms underlying LUSC, and identifying 3-lncRNA signature may serve as a potentially prognostic biomarker in predicting the OS of LUSC patients.

SUBMITTER: Hu J

PROVIDER: S-EPMC6835103 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Systematic analysis identifies three-lncRNA signature as a potentially prognostic biomarker for lung squamous cell carcinoma using bioinformatics strategy.

Hu Jing J Xu Lutong L Shou Tao T Chen Qiang Q

Translational lung cancer research 20191001 5

<h4>Background</h4>Lung squamous cell carcinoma (LUSC) is the second most common histological subtype of lung cancer (LC), and the prognoses of most LUSC patients are so far still very poor. The present study aimed at integrating lncRNA, miRNA and mRNA expression data to identify lncRNA signature in competitive endogenous RNA (ceRNA) network as a potentially prognostic biomarker for LUSC patients.<h4>Methods</h4>Gene expression data and clinical characteristics of LUSC patients were retrieved fr ...[more]

PMID: 31737498

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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:Mounting evidence has demonstrated that a lot of miRNAs are overexpressed or downregulated in colorectal cancer (CRC) tissues and play a crucial role in tumorigenesis, invasion, and migration. The aim of our study was to screen new biomarkers related to CRC prognosis by bioinformatics analysis. By using the R language edgeR package for the differential analysis and standardization of miRNA expression profiles from The Cancer Genome Atlas (TCGA), 502 differentially expressed miRNAs (343 up-regulated, 159 down-regulated) were screened based on the cut-off criteria of p < 0.05 and |log2FC|>1, then all the patients (421) with differentially expressed miRNAs and complete survival time, status were then randomly divided into train group (212) and the test group (209). Eight miRNAs with p < 0.005 were revealed in univariate cox regression analysis of train group, then stepwise multivariate cox regression was applied for constituting a five-miRNA (hsa-miR-5091, hsa-miR-10b-3p, hsa-miR-9-5p, hsa-miR-187-3p, hsa-miR-32-5p) signature prognostic biomarkers with obviously different overall survival. Test group and entire group shown the same results utilizing the same prescient miRNA signature. The area under curve (AUC) of receiver operating characteristic (ROC) curve for predicting 5 years survival in train group, test group, and whole cohort were 0.79, 0.679, and 0.744, respectively, which demonstrated better predictive power of prognostic model. Furthermore, Univariate cox regression and multivariate cox regression considering other clinical factors displayed that the five-miRNA signature could serve as an independent prognostic factor. In order to predict the potential biological functions of five-miRNA signature, target genes of these five miRNAs were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway and Gene Ontology (GO) enrichment analysis. The top 10 hub genes (ESR1, ADCY9, MEF2C, NRXN1, ADCY5, FGF2, KITLG, GATA1, GRIA1, KAT2B) of target genes in protein protein interaction (PPI) network were screened by string database and Cytoscape 3.6.1 (plug-in cytoHubba). In addition, 19 of target genes were associated with survival prognosis. Taken together, the current study showed the model of five-miRNA signature could efficiently function as a novel and independent prognosis biomarker and therapeutic target for CRC patients.

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Systematic analysis identifies three-lncRNA signature as a potentially prognostic biomarker for lung squamous cell carcinoma using bioinformatics strategy.

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Systematic analysis identifies three-lncRNA signature as a potentially prognostic biomarker for lung squamous cell carcinoma using bioinformatics strategy.

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