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Published on: July 22, 2020
Identification of potential core genes in gastric cancer using bioinformatics analysis
Changjiang Shao1,2, Rong Wang3, Dandan Kong3
1Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Background:
Gastric cancer is the third leading cause of cancer-related mortality in China. Most patients with gastric cancer have no obvious early symptoms; thus, many of them are in the middle and late stages of gastric cancer at first diagnosis and miss the best treatment opportunity. Molecular targeted therapy is particularly important in changing this status quo.
Methods:
Three microarray datasets (GSE29272, GSE33651, and GSE54129) were selected from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened using GEO2R. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to analyze the functional features of these DEGs and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The protein-protein interaction (PPI) of these DEGs was visualized by Cytoscape software. The expressions of hub genes were evaluated based on Gene Expression Profiling Interactive Analysis (GEPIA). Moreover, we used the online Kaplan-Meier plotter survival analysis tool to evaluate the prognostic values of hub genes. The Target Scan database was used to predict microRNAs that could regulate the target gene, collagen type IV alpha 1 chain (COL4A1). The OncomiR database was used to analyze the expression levels of three microRNAs, as well as the relationships with tumor stage, grade, and prognosis.
Results:
We identified 78 DEGs, including 53 upregulated genes and 25 downregulated genes. The DEGs were mainly enriched in extracellular matrix organization, extracellular structure organization, and response to wounding. Moreover, three KEGG pathways were markedly enriched, including focal adhesion, complement and coagulation cascades, and extracellular matrix (ECM)-receptor interaction. Among these 78 genes, we selected 10 hub genes. The overexpression levels of these hub genes were closely related to poor prognosis and the development of gastric cancer (except for COL3A1, LOX, and CXCL8). Moreover, we found that microRNA-29a-3p, miR-29b-3p, and miR-29c-3p were the potential microRNAs that could regulate the target gene, COL4A1.
Conclusions:
Our results showed that FN1, COL1A1, TIMP1, COL1A2, SPARC, COL4A1, and SERPINE1 could contribute to the development of novel molecular targets and biomarker-driven treatments for gastric cancer.
Insights
This study identifies key genes and microRNAs involved in gastric cancer progression. These findings may lead to new molecular targeted therapies and biomarkers for early detection and treatment of this deadly disease.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Gastric cancer is a leading cause of cancer mortality in China.
- Late diagnosis due to asymptomatic nature leads to missed treatment opportunities.
- Molecular targeted therapy offers a promising approach to improve outcomes.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) in gastric cancer.
- To analyze the functional enrichment and pathways of DEGs.
- To investigate the prognostic value of hub genes and their regulatory microRNAs.
Main Methods:
- Analysis of three Gene Expression Omnibus (GEO) datasets (GSE29272, GSE33651, GSE54129).
- Identification of DEGs using GEO2R, functional enrichment with DAVID, and pathway analysis (KEGG).
- Protein-protein interaction network construction (Cytoscape), hub gene expression analysis (GEPIA), survival analysis, and microRNA prediction (TargetScan, OncomiR).
Main Results:
- Identified 78 DEGs (53 upregulated, 25 downregulated) enriched in extracellular matrix organization and related pathways.
- Ten hub genes were identified, with most overexpressed genes correlating with poor gastric cancer prognosis.
- MicroRNAs miR-29a-3p, miR-29b-3p, and miR-29c-3p were predicted to regulate COL4A1.
Conclusions:
- Identified FN1, COL1A1, TIMP1, COL1A2, SPARC, COL4A1, and SERPINE1 as potential therapeutic targets.
- These genes may serve as biomarkers for gastric cancer diagnosis and prognosis.
- Findings support the development of novel molecular targeted therapies for gastric cancer.
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