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Integrated Bioinformatics Analysis Identifies Hub Genes Associated with the Pathogenesis and Prognosis of Esophageal Squamous Cell Carcinoma.

ABSTRACT: Esophageal squamous cell carcinoma (ESCC) accounts for over 90% of all esophageal tumors. However, the molecular mechanism underlying ESCC development and prognosis remains unclear, and there are still no effective molecular biomarkers for diagnosing or predicting the clinical outcome of patients with ESCC. Here, using bioinformatics analyses, we attempted to identify potential biomarkers and therapeutic targets for ESCC. Differentially expressed genes (DEGs) between ESCC and normal esophageal tissue samples were obtained through comprehensive analysis of three publicly available gene expression profile datasets from the Gene Expression Omnibus database. The biological roles of the DEGs were identified by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Moreover, the Cytoscape 3.7.1 platform and subsidiary tools such as Molecular Complex Detection (MCODE) and CytoHubba were used to visualize the protein-protein interaction (PPI) network of the DEGs and identify hub genes. A total of 345 DEGs were identified between normal esophageal and ESCC samples, which were enriched in the KEGG pathways of the cell cycle, endocytosis, pancreatic secretion, and fatty acid metabolism. Two of the highest scoring models were selected from the PPI network using Molecular Complex Detection. Moreover, CytoHubba revealed 21 hub genes with a valuable influence on the progression of ESCC in these patients. Among these, the high expression levels of five genes-SPP1, SPARC, BGN, POSTN, and COL1A2-were associated with poor disease-free survival of ESCC patients, as indicated by survival analysis. Taken together, we identified that elevated expression of five hub genes, including SPP1, is associated with poor prognosis in ESCC patients, which may serve as potential prognostic biomarkers or therapeutic target for ESCC.

SUBMITTER: Zhang H

PROVIDER: S-EPMC6948276 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Integrated Bioinformatics Analysis Identifies Hub Genes Associated with the Pathogenesis and Prognosis of Esophageal Squamous Cell Carcinoma.

Zhang Hui H Zhong Jianing J Tu Youbing Y Liu Benquan B Chen Zhibo Z Luo Yunchen Y Tang Yaping Y Xiao Fei F Zhong Jincai J

BioMed research international 20191226

Esophageal squamous cell carcinoma (ESCC) accounts for over 90% of all esophageal tumors. However, the molecular mechanism underlying ESCC development and prognosis remains unclear, and there are still no effective molecular biomarkers for diagnosing or predicting the clinical outcome of patients with ESCC. Here, using bioinformatics analyses, we attempted to identify potential biomarkers and therapeutic targets for ESCC. Differentially expressed genes (DEGs) between ESCC and normal esophageal t ...[more]

PMID: 31950035

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Project description:ObjectiveThrough bioinformatics analysis methods, the public databases GEO and TCGA were used to research mRNA and squamous cell carcinoma of the esophagus, construct a lncRNA-mRNA network, and screen hub genes and lncRNAs related to prognosis.MethodDownload esophageal squamous cell carcinoma-related mRNA and lncRNA datasets GEO and TCGA public datasets, as well as clinical data, use bioinformatic tools to perform gene differential expression analysis on the datasets to obtain differentially expressing mRNA (DEmRNA) and lncRNA (DElncRNA), and plot volcano plots and cluster heatmaps. The differential intersection of differentially expressed DEmRNA and DElncRNA was extracted by Venn diagram and imported into CytoScape software, a regulatory network visualization software, to construct a lncRNA-mRNA network and use cytoHubba and MCODE plug-ins to screen hub genes and key lncRNAs. The DEmRNA in the network was imported into the Gene and Protein Interaction Retrieval Database (STRING), gene-encoded protein-protein interactions (PPI) network maps were created, and the genes in the PPI network maps were submitted to GO functional annotation and pathway enrichment analysis using Kyoto Encyclopedia of Gene Genomes (KEGG) (KEGG). The link between hub gene and prognosis was studied using the clinical data collected by TCGA.ResultRetrieve the datasets GSE23400 and GSE38129 from the GEO database and the esophageal squamous cell carcinoma-related mRNAs from TCGA databases and then obtain intersection. Differentially regulated genes revealed a correlation of 326 (up) with 191 (down) in terms of the differential intersection; for this study, we need to collect the GSE130078 dataset from GEO, as well as the lncRNAs from TCGA databases that are connected to esophageal squamous cell cancer. There were 184 differentially up- and downregulated genes in the differential intersection. A differential intersection network of the differential intersection lncRNA-mRNA network allowed us to identify the hub genes, including COL5A2 (COL3A1), COL1A1 (COL1A1), CTD-2171N6.1 (CTD-2171N6.1), and RP11-863P13.3 (RP11-863P13.3). The extracellular matrix, which is important in protein digestion and absorption, was shown to be the primary site of functional enrichment, as shown by GO/KEGG analysis. Squamous cell carcinoma of the mouth and throat is associated with a poor prognosis because of a change in the extracellular matrix structure caused by specific long noncoding RNA (lncRNA) regulatory upregulation.ConclusionFor the purpose of predicting the prognosis of cancer of the esophagus, researchers studied the esophageal squamous cell carcinoma-related hub genes and important noncoding RNAs (ncRNAs).

Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) as the main subtype of esophageal cancer (EC) is a leading cause of cancer-related death worldwide. Despite advances in early diagnosis and clinical management, the long-term survival of ESCC patients remains disappointing, due to a lack of full understanding of the molecular mechanisms.MethodsIn order to identify the differentially expressed genes (DEGs) in ESCC, the microarray datasets GSE20347 and GSE26886 from Gene Expression Omnibus (GEO) database were analyzed. The enrichment analyses of gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Set Enrichment Analysis (GSEA) were performed for the DEGs. The protein-protein interaction (PPI) network of these DEGs was constructed using the Cytoscape software based on the STRING database to select as hub genes for weighted co-expression network analysis (WGCNA) with ESCC samples from TCGA database.ResultsA total of 746 DEGs were commonly shared in the two datasets including 286 upregulated genes and 460 downregulated genes in ESCC. The DEGs were enriched in biological processes such as extracellular matrix organization, proliferation and keratinocyte differentiation, and were enriched in biological pathways such as ECM-receptor interaction and cell cycle. GSEA analysis also indicated the enrichment of upregulated DEGs in cell cycle. The 40 DEGs were selected as hub genes. The MEblack module was found to be enriched in the cell cycle, Spliceosome, DNA replication and Oocyte meiosis. Among the hub genes correlated with MEblack module, GSEA analysis indicated that DEGs of TCGA samples with DLGAP5 upregulation was enriched in cell cycle. Moreover, the highly endogenous expression of DLGAP5 was confirmed in ESCC cells. DLGAP5 knockdown significantly inhibited the proliferation of ESCC cells.ConclusionsDEGs and hub genes such as DLGAP5 from independent datasets in the current study will provide clues to elucidate the molecular mechanisms involved in development and progression of ESCC.

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Integrated Bioinformatics Analysis Identifies Hub Genes Associated with the Pathogenesis and Prognosis of Esophageal Squamous Cell Carcinoma.

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Integrated Bioinformatics Analysis Identifies Hub Genes Associated with the Pathogenesis and Prognosis of Esophageal Squamous Cell Carcinoma.

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