Identification of significant biomarkers and pathways associated with gastric carcinogenesis by whole genome-wide expression profiling analysis

Abstract

The incidence of gastric cancer (GC) is extremely high in East Asia. GC is also one of the most common and lethal forms of cancer from a global perspective. However, to date, we have not been able to determine one or several genes as biomarkers in the diagnosis of GC and have also been unable to identify the genes which are important in the therapy of GC. In this study, we analyzed all genome-wide expression profiling arrays uploaded onto the Gene Expression Omnibus (GEO) database to filtrate the differentially expressed genes (DEGs) between normal stomach tissues and GC tissues. GSE13911, GSE19826 and GSE79973 were based on the GPL570 platform, and GSE29272 was based on the GPL96 platform. We screened out the DEGs from the two platforms and by selecting the intersection of these two platforms, we identified the common DEGs in the sequencing data from different laboratories. Finally, we obtained 3 upregulated and 34 downregulated DEGs in GC from 384 samples. As the number of downregulated DEGs was greater than that of the upregulated DEGs, functional analysis and pathway enrichment analysis were performed on the downregulated DEGs. Through our analysis, we identified the most significant genes associated with GC, such as secreted phosphoprotein 1 (SPP1), sulfatase 1 (SULF1), thrombospondin 2 (THBS2), ATPase H+/K+ transporting beta subunit (ATP4B), gastric intrinsic factor (GIF) and gastrokine 1 (GKN1). The prognostic power of these genes was corroborated in the Oncomine database and by Kaplan-Meier plotter (KM-plotter) analysis. Moreover, gastric acid secretion, collecting duct acid secretion, nitrogen metabolism and drug metabolism were significantly related to GC. Thus, these genes and pathways may be potential targets for improving the diagnosis and clinical effects in patients with GC.

Identification of potential key genes in gastric cancer using bioinformatics analysis

“…They regulate gastric acid secretion and, as a result, are targets for acid reduction (63). Fei et al (64) found that expression of ATP4A and ATP4B were significantly downregulated in patients with GC, but their expression was not significantly correlated with overall survival (64). In the present study, downregulation of ATP4A and ATP4B expression was associated with favorable overall survival in patients with GC.…”

Identification and analysis of genes associated with head and neck squamous cell carcinoma by integrated bioinformatics methods

“…For example, the usage of two GEO datasets provided a novel understanding of the mechanism underlying breast cancer metastasis to the brain and provided potential therapeutic targets (Tang, Zhao, Zhang, Wang, & Wang, ). Additionally, by analyzing the original data (GSE13911, GSE19826, GSE79973 and GSE29272) from the GEO database, the most significant genes and pathways associated with gastric cancer were identified, providing potential therapeutic targets to improve the clinical effects in patients with gastric cancer (Fei et al, ). What is more, dysregulated genes identified from four independent GEO datasets were found to be closely associated with hepatocellular carcinoma progression and may be exploited as potential biomarkers for diagnosis and prognosis (Yin et al, ).…”

ATP4B suppresses cell proliferation and migration via mitochondrial/p53/NF-κB pathway in gastric cancer

“…In recent years, several different algorithms are used to select feature genes based on differential expression profiling data of GC and a large number of GC candidate biomarkers and related gene signatures have been identified [5]. It has been reported that ATP4B, COL1A2 and HADHSC are the promising biomarkers [6][7][8]. ATP4B is diagnostically significant with apparent fold-changes in our previous study [9].…”