Abstract
BackgroundEsophageal squamous cell carcinoma (ESCC) has become one of the most serious diseases affecting populations worldwide and is the primary subtype of esophageal cancer (EC). However, the molecular mechanisms governing the development of ESCC have not been fully elucidated.Methods The robust rank aggregation method was performed to identify the differentially expressed genes (DEGs) in six datasets (GSE17351, GSE20347, GSE23400, GSE26886, GSE38129 and GSE77861) from the Gene Expression Omnibus (GEO). The Search Tool for the Retrieval of Interacting Genes (STRING) database was utilized to extract four hub genes from the protein–protein interaction (PPI) network. Module analysis and disease free survival analysis of the four hub genes were performed by Cytoscape and GEPIA. The expression of hub genes was analyzed by GEPIA and the Oncomine database and verified by real-time quantitative PCR (qRT-PCR).ResultsIn total, 720 DEGs were identified in the present study; these genes consisted of 302 upregulated genes and 418 downregulated genes that were significantly enriched in the cellular component of the extracellular matrix part followed by the biological process of the cell cycle phase and nuclear division. The primary enriched pathways were hsa04110:Cell cycle and hsa03030:DNA replication. Four hub genes were screened out, namely, SPP1, MMP12, COL10A1 and COL5A2. These hub genes all exhibited notably increased expression in ESCC samples compared with normal samples, and ESCC patients with upregulation of all four hub genes exhibited worse disease free survival.ConclusionsSPP1, MMP12, COL10A1 and COL5A2 may participate in the tumorigenesis of ESCC and demonstrate the potential to serve as molecular biomarkers in the early diagnosis of ESCC. This study may help to elucidate the molecular mechanisms governing ESCC and facilitate the selection of targets for early treatment and diagnosis.
Highlights
Esophageal squamous cell carcinoma (ESCC) has become one of the most serious diseases affecting populations worldwide and is the primary subtype of esophageal cancer (EC)
The PCR process was done on an ABI PRISM 7500 real-time PCR system
The Gene Ontology (GO) categories of molecular function (MF), biological process (BP) and cellular component (CC) for differentially expressed genes (DEGs) were significantly enriched, and the top 12 GO terms of the DEGs with upregulation and downregulation are listed in Additional file 2: Table S2
Summary
Esophageal squamous cell carcinoma (ESCC) has become one of the most serious diseases affecting populations worldwide and is the primary subtype of esophageal cancer (EC). Using systematic analysis of gene expression can rapidly filter DEGs that may have important effects on cancer progression [14]. The data from these public databases may help to characterize the development and molecular mechanism of ESCC after reanalysis. It is urgently important to identify effective molecular biomarkers that will be crucial to the diagnosis and treatment of ESCC patients, and the hub genes in ESCC along with the biological pathways associated with the DEGs are investigated in the present study
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