Abstract
BackgroundEsophageal squamous cell carcinoma (ESCC) is one of leading malignant cancers of gastrointestinal tract worldwide. Until now, the involved mechanisms during the development of ESCC are largely unknown. This study aims to explore the driven-genes and biological pathways in ESCC.MethodsmRNA expression datasets of GSE29001, GSE20347, GSE100942, and GSE38129, containing 63 pairs of ESCC and non-tumor tissues data, were integrated and deeply analyzed. The bioinformatics approaches include identification of differentially expressed genes (DEGs) and hub genes, gene ontology (GO) terms analysis and biological pathway enrichment analysis, construction and analysis of protein–protein interaction (PPI) network, and miRNA–gene network construction. Subsequently, GEPIA2 database and qPCR assay were utilized to validate the expression of hub genes. DGIdb database was performed to search the candidate drugs for ESCC.ResultsFinally, 120 upregulated and 26 downregulated DEGs were identified. The functional enrichment of DEGs in ESCC were mainly correlated with cell cycle, DNA replication, deleted in colorectal cancer (DCC) mediated attractive signaling pathway, and Netrin-1 signaling pathway. The PPI network was constructed using STRING software with 146 nodes and 2392 edges. The most significant three modules in PPI were filtered and analyzed. Totally ten genes were selected and considered as the hub genes and nuclear division cycle 80 (NDC80) was closely related to the survival of ESCC patients. DGIdb database predicted 33 small molecules as the possible drugs for treating ESCC.ConclusionsIn summary, the data may provide new insights into ESCC pathogenesis and treatments. The candidate drugs may improve the efficiency of personalized therapy in future.
Highlights
Esophageal squamous cell carcinoma (ESCC) is one of leading malignant cancers of gastrointestinal tract worldwide
Enrichment analysis and protein–protein interaction (PPI) network Functional enrichment analysis of differentially expressed genes (DEGs) gene ontology (GO) and pathways enrichment were analyzed through multiple databases or software, including DAVID [18], Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway [29], and FunRich software [19] with p < 0.05 as the cut-off criterion
Using integrated bioinformatics analysis, the study identified commonly changed 146 DEGs in ESCC, which were enriched in DNA replication, cell cycle, deleted in colorectal cancer (DCC) mediated pathway, and Netrin-1 signaling pathway
Summary
Esophageal squamous cell carcinoma (ESCC) is one of leading malignant cancers of gastrointestinal tract worldwide. The involved mechanisms during the development of ESCC are largely unknown. EC includes two most common histologic subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) [2]. ESCC comprises over 90% of all EC cases [1]. The underlying mechanisms of ESCC are not well understood. Due to the lack of specific biomarkers, most ESCC patients are diagnosed at a late stage, leading to poor outcomes of patients [3]. Some of ESCC patients suffer from tumor recurrence due to the chemotherapy resistance [3]. It is of paramount importance to find novel biomarkers and effective targets for ESCC patients
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