Identification of Hub Genes Associated With the Development of Stomach Adenocarcinoma by Integrated Bioinformatics Analysis

Abstract

ObjectiveThis study was conducted in order to gain a better understanding of the molecular mechanisms of stomach adenocarcinoma (STAD), which is necessary to predict the prognosis of STAD and develop novel gene therapy strategies.MethodsIn this study, the gene expression profile of GSE118916 in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas Program (TCGA) was used to explore the differential co-expression genes of STAD and normal tissues.ResultsA total of 407 STAD samples were collected, consisting of 375 from stomach adenocarcinoma tissues and 32 from normal tissues, as well as RNA-seq count data for 19,600 genes. Forty-two differentially expressed genes were screened by weighted gene co-expression network analysis (WGCNA) and differentially expressed gene analysis. According to the functional annotation analysis of the clusterProfiler R package, these genes were analyzed for GO function enrichment, digestion (biological process), tube bottom material membrane (cell component), and oxidoreductase activity (molecular function). The KEGG pathway was enriched in gastric acid secretion and chemical carcinogenesis. In addition, Cytoscape’s cytoHubba plug-in was used to identify seven hub genes (EWSR1, ESR1, CLTC, PCMT1, TP53, HUWE1, and HDAC1) in a protein–protein interaction (PPI) network consisting of 7 nodes and 11 edges. Compared with normal tissues, CLTC and TP53 genes were upregulated in stomach adenocarcinoma (P < 0.05). TP53 was expressed differently in stages II and IV, EWSR1 was expressed differently in stages II and III, and ESR1 was expressed differently in stages I–III. Among the seven hub genes, Kaplan–Meier analysis and TCGG showed that the expression levels of HDAC1 and CLTC were significantly correlated with OS in patients with stomach adenocarcinoma (P < 0.05). GEPIA2 analysis showed that ESR1 expression was closely correlated with OS and DFS in gastric adenocarcinoma (P < 0.05). Then, the expression of the genes and their correlations were revealed by the R2 Platform (http://r2.amc.nl). Finally, we collected 18 pairs of gastric mucosal tissues from normal people and cancer tissues from patients with stomach adenocarcinoma. The expression levels of the above seven hub genes and their relative protein expression were detected by RT-PCR and immunohistochemistry (IHC). The results showed that the gene and protein expression levels in stomach adenocarcinoma tissues were increased than those in the normal group.ConclusionIn summary, we believe that the identified hub genes were related to the occurrence of stomach adenocarcinoma, especially the expression of ESR1, HDAC1, and CLTC genes, which are related to the prognosis and overall survival of patients and may become the potential for the future diagnosis and treatment of STAD.

Hub genes and pathways in gastric cancer: A comparison between studies that used normal tissues adjacent to the tumour and studies that used healthy tissues as calibrator

“…Also, the top protein module of the PPI network of the N and NAT list were enriched in the same KEGG terms. These KEGG terms were also reported for GC by Lu et al [20], who analysed seven microarray datasets with NAT tissues as calibrators, Sun et al [21], who analysed the TCGA database, Li et al [22], who analysed two microarray datasets, Zhang et al [23], who analysed three microarray datasets, and Zhang et al [24], who analysed one microarray dataset and TCGA database. Also, the GO enrichment analysis was shown that DEGs in the N and NAT lists were enriched in some similar terms, such as extracellular matrix organisation, retinol metabolism, and metabolism of xenobiotics by cytochrome P450.…”

“…[ 23 ], who analysed three microarray datasets, and Zhang et al. [ 24 ], who analysed one microarray dataset and TCGA database. Also, the GO enrichment analysis was shown that DEGs in the N and NAT lists were enriched in some similar terms, such as extracellular matrix organisation, retinol metabolism, and metabolism of xenobiotics by cytochrome P450.…”

Identification of Hub Genes Associated with the Progression and Prognosis of Gastric Cancer through Systematic Bioinformatics Analysis

“…GC is a malignant neoplasm affecting the gastrointestinal tract, characterized by a relatively high incidence and mortality. A signi cant proportion of patients present at an advanced stage upon diagnosis of GC, resulting in a 5-year survival rate ranging from only 11-40% [7]. Therefore, there is an urgent need for sensitive and speci c biomarkers for GC detection.…”

A systems biology approach to pathogenesis of gastric cancer: gene network modeling and pathway analysis

“…By integrated bioinformatics analysis in 2022, Zhang et al studied the stomach adenocarcinoma and introduced seven hub genes (EWSR1, ESR1, CLTC, PCMT1, TP53, HUWE1, and HDAC1) as related genes to occurrence of stomach adenocarcinoma [ 65 ]. Through a systems biology approach in 2022, Salarikia et al reported that medications such as pantoprazole, omeprazole, imatinib, troglitazone, fostamatinib, and amiloride might be useful in GC treatment.…”