Identification of Key Genes and Pathways in Triple-Negative Breast Cancer by Integrated Bioinformatics Analysis

Abstract

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.

<p>Construction and Comprehensive Analysis of a ceRNA Network to Reveal Potential Novel Biomarkers for Triple-Negative Breast Cancer</p>

“…TNBC-related studies have shown that these important GO aspects involved sister chromatid segregation, channel activity, passive transmembrane transporter activity, receptor regulator activity, extracellular matrix structural constituent and other aspects, and the results are consistent with the findings of previous TNBC-related studies. 4,54,55 Some new findings of our bioinformatics method require further study via experimental validation. Or analytical results showed that the influence of dysregulated mRNAs in the biological processes, cellular components, molecular functions and pathways may play pivotal roles in the pathogenesis of TNBC, all of which have been well documented.…”

Construction of a Novel 3-lncRNA Risk Score System for the Prognostic Prediction of Triple-Negative Breast Cancer

“…Tian et al [21]only used coexpression analysis of lncRNAs with mRNAs to identify lncRNAs in TNBC. Dong et al [22] identi ed the essential genes and pathways related to TNBC by DEGs and Protein-Protein Interaction (PPI) networks. These correlation network analyses only indicate whether multiple genes are related to each other.…”

Construct ion of co - expression modules related to survival by WGCNA and identif ication of potential prognostic biomarkers in glioblastoma

“…The five-year survival rate is still less than 10% [4][5][6]. Plenty of studies have been conducted to identify the underlying pathogenesis mechanisms, however, it's still not been illuminated [7][8][9]. In particular, there are few related studies on the expression modules of GBM, which has brought certain difficulties to the identification of key genes in the occurrence and recurrence of disease.…”