Abstract
Gastric cancer (GC) is one of the most common malignancies in the world, with morbidity and mortality ranking second among all cancers. Accumulating evidences indicate that circular RNAs (circRNAs) are closely correlated with tumorigenesis. However, the mechanisms of circRNAs still remain unclear. This study is aimed at determining hub genes and circRNAs and analyzing their potential biological functions in GC. Expression profiles of mRNAs and circRNAs were downloaded from the Gene Expression Omnibus (GEO) data sets of GC and paracancer tissues. Differentially expressed genes (DEGs) and differentially expressed circRNAs (DE-circRNAs) were identified. The target miRNAs of DE-circRNAs and the bidirectional interaction between target miRNAs and DEGs were predicted. Functional analysis was performed, and the protein-protein interaction (PPI) network and the circRNA-miRNA-mRNA network were established. A total of 456 DEGs and 2 DE-circRNAs were identified with 3 mRNA expression profiles and 2 circRNA expression profiles. GO analysis indicated that DEGs were mainly enriched in extracellular matrix and cell adhesion, and KEGG confirmed that DEGs were mainly associated with focal adhesion, the PI3K-Akt signaling pathway, extracellular matrix- (ECM)- receptor interaction, and gastric acid secretion. 15 hub DEGs (BGN, COL1A1, COL1A2, FBN1, FN1, SPARC, SPP1, TIMP1, UBE2C, CCNB1, CD44, CXCL8, COL3A1, COL5A2, and THBS1) were identified from the PPI network. Furthermore, the survival analysis indicate that GC patients with a high expression of the following 9 hub DEGs, namely, BGN, COL1A1, COL1A2, FBN1, FN1, SPARC, SPP1, TIMP1, and UBE2C, had significantly worse overall survival. The circRNA-miRNA-mRNA network was constructed based on 1 circRNA, 15 miRNAs, and 45 DEGs. In addition, the 45 DEGs included 5 hub DEGs. These results suggested that hub DEGs and circRNAs could be implicated in the pathogenesis and development of GC. Our findings provide novel evidence on the circRNA-miRNA-mRNA network and lay the foundation for future research of circRNAs in GC.
Highlights
Gastric cancer (GC) is one of the most common malignancies worldwide, with the morbidity and mortality of GC ranking second among all cancers, especially in East Asia, Eastern Europe, and South America [1]
The results indicated that 9 of the 15 hub Differentially expressed genes (DEGs) (FN1, SPARC, FBN1, BGN, UBE2C, SPP1, TIMP1, COL5A2, and CCNB1) in the protein-protein interaction (PPI) network were distributed in the three modules, suggesting that these genes may have important roles in GC
The results showed that nine hub DEGs (BGN, COL1A1, COL1A2, FBN1, FN1, SPARC, SPP1, TIMP1, and UBE2C) were associated with poor prognosis in GC patients (p < 0:05) (Figures 4(a)–4(i))
Summary
Gastric cancer (GC) is one of the most common malignancies worldwide, with the morbidity and mortality of GC ranking second among all cancers, especially in East Asia, Eastern Europe, and South America [1]. Much progress has been made in the diagnosis and treatment of GC, the 5-year overall survival rate remains poor (approximately 20-25%) [2]. There is an urgent need to study the mechanism underlying the occurrence and development of GC in order to achieve early diagnosis, effective treatment, and good prognosis for GC. Bioinformatics analysis, including the use of microarray expression data sets, protein/gene-protein/gene interaction networks, and gene annotation, can be used to study cancer progression and identify potential therapeutic targets for development [3]. Bioinformatics analysis methods can overcome the inconsistent results in the literature as a result of different sample sizes or microarray platforms in individual studies [4]. A large number of studies have used bioinformatics analysis to predict biomarkers for cancer treatments [5,6,7,8]
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