Dataset Information

Bioinformatics analysis of key genes in triple negative breast cancer and validation of oncogene PLK1.

ABSTRACT:

Background

Breast cancer is the most common malignancy in women. Triple-negative breast cancer (TNBC) refers to a special subtype that is deficient in the expression of estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER-2). In this study, a variety of bioinformatics analysis tools were used to screen Hub genes related to the occurrence and development of triple negative breast cancer, and their biological functions were analyzed.

Methods

Gene Expression Omnibus (GEO) breast cancer microarray data GSE62931 was selected as the research object. The differentially expressed genes (DEGs) were screened and the protein-protein interaction (PPI) network of DEGs was constructed using bioinformatics tools. The Hub genes were also screened. The Gene Ontology (GO) knowledgebase and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for biological enrichment analysis. The Gene Expression Profiling Interactive Analysis (GEPIA) online tool was used to verify the expression of the screened genes and patient survival. The effects of polo-like kinase 1 (PLK1) on the proliferation, invasion, migration, and dryness of breast cancer cells were verified using cell counting kit 8 (CCK-8), transwell migration assays, scratch tests, and clone formation tests. An animal model of subcutaneous xenotransplantation of breast cancer was established to evaluate the effect of PLK1 on the proliferation of breast cancer.

Results

A total of 824 DEGs were screened by GSE62931 microarray data; 405 of which were up-regulated and 419 of which were down-regulated. Functional enrichment analysis showed that these DEGs were mainly enriched in cancer-related pathways and were primarily involved in biological processes (BP) such as cell and mitotic division. From the Hub gene screening, PLK1 was further identified as the Hub gene associated with TNBC. Cell and animal experiments indicated that PLK1 promotes the proliferation, invasion, migration, and clone formation of breast cancer cells.

Conclusions

Gene chip combined with bioinformatics methods can effectively analyze the DEGs related to the occurrence and development of breast cancer, and the screening of PLK1 can provide theoretical guidance for further research on the molecular mechanism of breast cancer and the screening of molecular markers.

SUBMITTER: Ren Y

PROVIDER: S-EPMC7812170 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Bioinformatics analysis of key genes in triple negative breast cancer and validation of oncogene PLK1.

Ren Yi Y Deng Rong R Zhang Qian Q Li Jing J Han Baosan B Ye Ping P

Annals of translational medicine 20201201 24

<h4>Background</h4>Breast cancer is the most common malignancy in women. Triple-negative breast cancer (TNBC) refers to a special subtype that is deficient in the expression of estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER-2). In this study, a variety of bioinformatics analysis tools were used to screen Hub genes related to the occurrence and development of triple negative breast cancer, and their biological functions were analyzed.<h4>Methods</h4>Gene Expre ...[more]

PMID: 33490149

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Project description:Purpose:Triple-negative breast cancer refers to breast cancer that does not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (Her2). This study aimed to identify the key pathways and genes and find the potential initiation and progression mechanism of triple-negative breast cancer (TNBC). Methods:We downloaded the gene expression profiles of GSE76275 from Gene Expression Omnibus (GEO) datasets. This microarray Super-Series sets are composed of gene expression data from 265 samples which included 67 non-TNBC and 198 TNBC. Next, all the differentially expressed genes (DEGs) with p<0.01 and fold change ?1.5 or ?-1.5 were identified. Result:56 upregulated and 151 downregulated genes were listed and the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis was performed. These significantly changed genes were mainly involved in the biological process termed prostate gland morphogenesis, inner ear morphogenesis, cell maturation, digestive tract morphogenesis, autonomic nervous system development, monovalent inorganic anion homeostasis, neural crest cell development, regulation of dendrite extension and glial cell proliferation, immune system process termed T cell differentiation, regulation of immune response, and macrophage activation. Genes are mainly involved in the KEGG pathway termed Oocyte meiosis. All DEGs underwent survival analysis using datasets from The Cancer Genome Atlas (TCGA) integrated by cBioPortal, of which amplification of SRY-related HMG-box 8 (SOX8), androgen receptor (AR), and Chromosome 9 Open Reading Frame 152 (C9orf152) were significantly negative while Nik Related Kinase (NRK) and RAS oncogene family 30 (RAB30) were positively correlated to the life expectancy (p<0.05). Conclusions:In conclusion, these pathways and genes identified could help understanding the mechanism of development of TNBC. Besides, SOX8, AR, C9orf152, NRK and RAB30, and other key genes and pathways might be promising targets for the TNBC treatment.

Project description:BackgroundTreatment strategies for various subtypes of breast cancer (BC) are different based on their distinct molecular characteristics. Therefore, it is very important to identify key differentially expressed genes (DEGs) between ER-positive/HER2-negative BC and ER-negative/HER2-negative BC.MethodsGene expression profiles of GSE22093 and GSE23988 were obtained from the Gene Expression Omnibus database. There were 74 ER-positive/HER2-negative BC tissues and 85 ER-negative/HER2-negative BC tissues in the two profile datasets. DEGs between ER-positive/HER2-negative tissues and ER-negative/HER2-negative BC tissues were identified by the GEO2R tool. The common DEGs among the two datasets were detected with Venn software online. Next, we made use of the Database for Annotation, Visualization and Integrated Discovery to analyze enriched Kyoto Encyclopedia of Gene and Genome (KEGG) pathways and gene ontology terms. Then, the protein-protein interactions (PPIs) of these DEGs were visualized by Cytoscape with the Search Tool for the Retrieval of Interacting Genes. Of the proteins in the PPI network, Molecular Complex Detection plug-in analysis identified nine core upregulated genes and one core downregulated gene. UALCAN and Gene Expression Profiling Interactive Analysis were applied to determine the expression of these 10 genes in BC. Furthermore, for the analysis of overall survival among those genes, the Kaplan-Meier method was implemented.ResultsNinety-three common DEGs (63 upregulated and 30 downregulated) were identified. KEGG pathway enrichment analysis showed that upregulated DEGs were particularly enriched in the progesterone-mediated oocyte maturation pathway. In addition, PGR might be a prognostic biomarker for ER-positive/HER2-negative BC. CCND1 is a poor prognostic biomarker for ER-positive/HER2-negative BC and ER-negative/HER2-negative BC. Moreover, TFF1, AGR2 and EGFR might be predictive biomarkers of node metastasis in ER-positive/HER2-negative BC and ER-negative/HER2-negative BC.ConclusionsCCND1, AGR2, PGR, TFF1 and EGFR are the key DEGs between ER-positive/HER2-negative BC and ER-negative/HER2-negative BC. Further studies are required to confirm the functions of the identified genes.

Dataset Information

Bioinformatics analysis of key genes in triple negative breast cancer and validation of oncogene PLK1.

Background

Methods

Results

Conclusions

Publications

Bioinformatics analysis of key genes in triple negative breast cancer and validation of oncogene PLK1.

Similar Datasets

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