Abstract
BackgroundGastric carcinoma (GC) is one of the most common cancer globally. Despite its worldwide decline in incidence and mortality over the past decades, gastric cancer still has a poor prognosis. However, the key regulators driving this process and their exact mechanisms have not been thoroughly studied. This study aimed to identify hub genes to improve the prognostic prediction of GC and construct a messenger RNA-microRNA-long non-coding RNA(mRNA-miRNA-lncRNA) regulatory network.MethodsThe GSE66229 dataset, from the Gene Expression Omnibus (GEO) database, and The Cancer Genome Atlas (TCGA) database were used for the bioinformatic analysis. Differential gene expression analysis methods and Weighted Gene Co-expression Network Analysis (WGCNA) were used to identify a common set of differentially co-expressed genes in GC. The genes were validated using samples from TCGA database and further validation using the online tools GEPIA database and Kaplan-Meier(KM) plotter database. Gene set enrichment analysis(GSEA) was used to identify hub genes related to signaling pathways in GC. The RNAInter database and Cytoscape software were used to construct an mRNA-miRNA-lncRNA network.ResultsA total of 12 genes were identified as the common set of differentially co-expressed genes in GC. After verification of these genes, 3 hub genes, namely CTHRC1, FNDC1, and INHBA, were found to be upregulated in tumor and associated with poor GC patient survival. In addition, an mRNA-miRNA-lncRNA regulatory network was established, which included 12 lncRNAs, 5 miRNAs, and the 3 hub genes.ConclusionsIn summary, the identification of these hub genes and the establishment of the mRNA-miRNA-lncRNA regulatory network provide new insights into the underlying mechanisms of gastric carcinogenesis. In addition, the identified hub genes, CTHRC1, FNDC1, and INHBA, may serve as novel prognostic biomarkers and therapeutic targets.
Highlights
Gastric carcinoma (GC) is a common malignant tumor originating from the gastric mucosal epithelium
This study aimed to identify hub genes to improve the prognostic prediction of GC and construct a messenger RNA-microRNA-long non-coding RNA regulatory network
Sha et al [11] found that ORAI2 promotes gastric cancer cell migration and tumor metastasis through MAPK-dependent focal adhesion disassembly and PI3K/Akt signaling, which suggests the possibility of developing potential therapies for GC by targeting the ORAI2 signaling pathway
Summary
Gastric carcinoma (GC) is a common malignant tumor originating from the gastric mucosal epithelium. Despite its worldwide decline in incidence and mortality rates over the past decades, GC has a poor prognosis [1]. The pathogenesis of gastric cancer remains unclear to date, gastric cancer is widely considered to be a highly heterogeneous disease caused by multiple factors, including chronic infection with Helicobacter pylori [3, 4], Epstein–Barr virus [5], unhealthy diet [6], smoking [7], etc., which interact with genes and lead to tumor development [8, 9]. Sha et al [11] found that ORAI2 promotes gastric cancer cell migration and tumor metastasis through MAPK-dependent focal adhesion disassembly and PI3K/Akt signaling, which suggests the possibility of developing potential therapies for GC by targeting the ORAI2 signaling pathway. Despite its worldwide decline in incidence and mortality over the past decades, gastric cancer still has a poor prognosis. This study aimed to identify hub genes to improve the prognostic prediction of GC and construct a messenger RNA-microRNA-long non-coding RNA (mRNA-miRNA-lncRNA) regulatory network
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