Dataset Information

[BUB1 gene is highly expressed in gastric cancer:analysis based on Oncomine database and bioinformatics].

ABSTRACT: OBJECTIVE:To investigate the expression of BUB1 gene in gastric cancer. METHODS:Oncomine, GEPIA, BioGPS and Kaplan-Meier Plotter databases were used to analyze the difference of BUB1 gene expression between gastric cancer tissue and normal gastric tissue. The association of BUB1 expression level with the prognosis of gastric cancer patients was also analyzed. The Cancer Cell Line Encyclopedia (CCLE) was explored to analyze the expression of BUB1 in T cells and B cells in gastric cancer patients, and the String database was used to generate the network map of BUB1-related proteins and functional annotation of gene ontology (GO). The related pathways of KEGG were analyzed. Tumor immune assessment resource (TIMER) database was used to analyze the expression of BUB1 in immune infiltration and its effect on prognosis of gastric cancer patients. To further verify the results of gene chip analysis in Oncomine database, we collected 30 pairs of surgical specimens of gastric adenocarcinoma and adjacent tissues from patients admitted to the First Affiliated Hospital of Chengdu Medical College from March, 2018 to July, 2019. The results of BUB1 gene expression in Oncomine database were verified by PCR and immunohistochemistry. RESULTS:Oncomine, GEPIA and BioGPS analyses showed that BUB1 was highly expressed in gastric cancer compared with normal gastric tissue. Kaplan-Meier survival analysis showed that the progression-free survival time (HR=0.52, 95% CI:0.41-0.67, P < 0.05) and the overall survival time (HR=0.67, 95% CI:0.55-0.82, P < 0.05) were prolonged in gastric cancer patients with a high expression of BUB1. Through String data collection, BUB1-related proteins were mainly enriched in 13 cellular components, 4 molecular functions and 12 biological processes, involving 4 signal pathways. TIMER database analysis showed that CD4+ T cells and macrophages with high expressions of BUB1 mRNA in the immune microenvironment were associated with a favorable 5-year survival outcome of patients with gastric cancer. In the surgical specimens, real-time quantitative PCR showed that the expression level of BUB1 mRNA was significantly higher in gastric cancer tissues than in the adjacent gastric mucosa tissues, and immunohistochemical results demonstrated positive BUB1 staining in the gastric cancer tissues. CONCLUSIONS:BUB1 gene is highly expressed in gastric cancer. BUB1 may reduce tumor immunosuppression and helps to evaluate the prognosis of patients with gastric cancer.

SUBMITTER: Li X

PROVIDER: S-EPMC7277308 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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[BUB1 gene is highly expressed in gastric cancer:analysis based on Oncomine database and bioinformatics].

Li Xiaoyan X He Jie J Yu Mi M Zhang Wei W Sun Jian J

Nan fang yi ke da xue xue bao = Journal of Southern Medical University 20200501 5

<h4>Objective</h4>To investigate the expression of BUB1 gene in gastric cancer.<h4>Methods</h4>Oncomine, GEPIA, BioGPS and Kaplan-Meier Plotter databases were used to analyze the difference of BUB1 gene expression between gastric cancer tissue and normal gastric tissue. The association of BUB1 expression level with the prognosis of gastric cancer patients was also analyzed. The Cancer Cell Line Encyclopedia (CCLE) was explored to analyze the expression of BUB1 in T cells and B cells in gastric c ...[more]

PMID: 32897212

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Project description:Background: Gastric cancer (GC) has a high mortality rate in cancer-related deaths worldwide. Currently, the pathogenesis of gastric cancer progression remains unclear. Here, we identified several vital candidate genes related to gastric cancer development and revealed the potential pathogenic mechanisms using integrated bioinformatics analysis. Methods: Two microarray datasets from Gene Expression Omnibus (GEO) database integrated. Limma package was used to analyze differentially expressed genes (DEGs) between GC and matched normal specimens. DAVID was utilized to conduct Gene ontology (GO) and KEGG enrichment analysis. The relative expression of OLFM4, IGF2BP3, CLDN1 and MMP1were analyzed based on TCGA database provided by UALCAN. Western blot and quantitative real time PCR assay were performed to determine the protein and mRNA levels of OLFM4, IGF2BP3, CLDN1 and MMP1 in GC tissues and cell lines, respectively. Results: We downloaded the expression profiles of GSE103236 and GSE118897 from the Gene Expression Omnibus (GEO) database. Two integrated microarray datasets were used to obtain differentially expressed genes (DEGs), and bioinformatics methods were used for in-depth analysis. After gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analysis, we identified 61 DEGs in common, of which the expression of 34 genes were elevated and 27 genes were decreased. GO analysis displayed that the biological functions of DEGs mainly focused on negative regulation of growth, fatty acid binding, cellular response to zinc ion and calcium-independent cell-cell adhesion. KEGG pathway analysis demonstrated that these DEGs mainly related to the Wnt and tumor signaling pathway. Interestingly, we found 4 genes were most significantly upregulated in the DEGs, which were OLFM4, IGF2BP3, CLDN1 and MMP1. Then, we confirmed the upregulation of these genes in STAD based on sample types. In the final, western blot and qRT-PCR assay were performed to determine the protein and mRNA levels of OLFM4, IGF2BP3, CLDN1 and MMP1 in GC tissues and cell lines. Conclusion: In our study, using integrated bioinformatics to screen DEGs in gastric cancer could benefit us for understanding the pathogenic mechanism underlying gastric cancer progression. Meanwhile, we also identified four significantly upregulated genes in DEGs from both two datasets, which might be used as the biomarkers for early diagnosis and prevention of gastric cancer.

Project description:Gastric cancer (GC) is the fifth most common cancer and GC has a high mortality rate worldwide. Circular (circ) RNAs serve an important role in cancer. The present study aimed to investigate the expression level of hsa_circ_0060975 in gastric cancer (GC) and to determine the clinical pathological significance of hsa_circ_0060975 in patients with GC. Reverse transcription-quantitative PCR was used to detect expression level of hsa_circ_0060975 in 192 GC and adjacent non-cancerous gastric tissues, in GC cell lines (MKN-45, HGC27 and AGS) and a human gastric epithelium cell line (GES-1), as well as in plasma samples from 126 patients with GC and 92 healthy volunteers. All plasma and tissue samples of were obtained from The First Affiliated Hospital of Anhui Medical University (Hefei, China). The relationship between hsa_circ_0060975 expression and clinical pathological factors was analyzed using the χ2 test. The diagnostic value of hsa_circ_0060975 was analyzed using the receiver operating characteristic curve (ROC curve), while the Kaplan-Meier method was used to analyze the relationship of hsa_circ_0060975 expression with the survival of patients with GC as determined by log-rank tests. Univariate and multivariate Cox regression analyses were used to identify the prognostic factors, including hsa_circ_0060975 expression and clinical pathological factors. In addition, the potential function of hsa_circ_0060975 was evaluated via bioinformatics analysis. The expression level of hsa_circ_0060975 was higher in GC tissues compared with adjacent non-cancerous gastric tissues, GC cell lines compared with GES-1 and plasma samples from patients with GC compared with plasma samples from healthy volunteers. In addition, higher hsa_circ_0060975 expression was associated with histological grade, pathological stage and tumor (T) classification in GC tissues and plasma samples (P<0.05). The area under the ROC curves of hsa_circ_0060975, the combination with hsa_circ_0060975 and carcinoembryonic antigen (CEA) or CEA alone were 0.804 (sensitivity, 0.746; specificity, 0.783; P<0.001); 0.931 (sensitivity, 0.937; specificity, 0.870; P<0.001) and 0.924 (sensitivity, 0.937; sspecificity, 0.804; P<0.001) respectively. The Kaplan-Meier survival analysis revealed that the overall survival (OS) and disease-free survival (DFS) time of patients with higher hsa_circ_0060975 expression were shorter compared with those in patients with lower hsa_circ_0060975 expression. Univariate and multivariate Cox regression analyses in OS and DFS time determined that the expression level of hsa_circ_0060975, histological grade and pathological stage were independent prognostic factors for patients with GC. In addition, the bioinformatics analysis results suggested that the abnormal expression of hsa_circ_0060975 may serve an important role in tumorigenesis. Hence, hsa_circ_0060975 expression may be an independent prognostic factor for patients with GC and may be a potential marker for biological malignancy.

Project description:BackgroundIncreasing evidence implicates circular RNAs (circRNAs) have been involved in human cancer progression. However, the mechanism remains unclear. In this study, we identified novel circRNAs related to gastric cancer and constructed a circRNA-miRNA-mRNA network.MethodsMicroarray datasets GSE83521 and GSE93541 were obtained from the Gene Expression Omnibus (GEO). Then, we used computational biology to identify circRNAs that were differentially expressed in both GC tissue and plasma compared to normal controls; then, we detected the expression of the selected circRNAs in gastric cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). We also identified circRNA-related candidate miRNAs and their target genes with online tools. Combining the predicted miRNAs and target mRNAs, a competing endogenous RNA regulatory network was established. Functional and pathway enrichment analyses were performed, and interactions between proteins were predicted by using String and Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to elucidate the possible functions of these differentially expressed circRNAs. The regulatory network constructed using the microarray datasets (GSE83521 and GSE93541) contained three differentially co-expressed circRNAs (DECs). A circRNA-miRNA-mRNA network was constructed based on 3 circRNAs, 43 miRNAs and 119 mRNAs.ResultsGO and KEGG analysis showed that the regulation of apoptotic signaling pathway and PI3K-Akt signaling pathway were highest degrees of enrichment respectively. We established a protein-protein interaction (PPI) network consisting of 165 nodes and 170 edges and identified hub genes by using MCODE plugin in Cytoscape. Furthermore, a core circRNA-miRNA-mRNA network was constructed based on hub genes. Hsa_circ_0001013 was finally determined to play an important role in the pathogenesis of GC according to the core circRNA-miRNA-mRNA network.ConclusionsWe propose a new circRNA-miRNA-mRNA network that is associated with the pathogenesis of GC. The network may become a new molecular biomarker and could be used to develop potential therapeutic strategies for gastric cancer.

Project description:Gastric adenocarcinoma (GAC), also known as stomach adenocarcinoma (STAD), is one of the most lethal malignancies in the world. It is vital to classify and detect the hub genes and key pathways participated in the initiation and progression of GAC. In this study, we collected and sequenced 15 pairs of GAC tumor tissues and the adjacent normal tissues. Differentially expressed genes (DEGs) were analyzed and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis were used to annotate the unique biological significance and important pathways of enriched DEGs. Moreover, we constructed the protein-protein interaction (PPI) network by Cytoscape and conducted KEGG enrichment analysis of the prime module. We further applied the TCGA database to start the survival analysis of these hub genes by Kaplan-Meier estimates. Finally, we obtained total 233 DEGs consisted of 64 up-regulated genes and 169 down-regulated genes. GO enrichment analysis found that DEGs most significantly enriched in single organism process, extracellular region, and extracellular region part. KEGG pathway enrichment analysis suggested that DEGs most significantly enriched in Protein digestion and absorption, Gastric acid secretion, and ECM-receptor interaction. Furthermore, the PPI network showed that the top 10 hub genes in GAC were IL8, COL1A1, MMP9, SST, COL1A2, TIMP1, FN1, SPARC, ALDH1A1, and SERPINE1 respectively. The prime gene interaction module in PPI network was enriched in protein digestion and absorption, ECM receptor interaction, the PI3K-Akt signaling pathway, and pathway in cancer. Survival analysis based on the TCGA database found that the expression of the FN1, SERPINE1, and SPARC significantly predicted poor prognosis of GAC. Collectively, we identified several hub genes and key pathways associated with GAC initiation and progression by analyzing the microarray data on DEGs, which provided a detailed molecular mechanism underlying GAC occurrence and progression.

Dataset Information

[BUB1 gene is highly expressed in gastric cancer:analysis based on Oncomine database and bioinformatics].

Publications

[BUB1 gene is highly expressed in gastric cancer:analysis based on Oncomine database and bioinformatics].

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