Identification of differentially expressed genes between triple and non-triple-negative breast cancer using bioinformatics analysis

Breast Cancer. 2019 Nov;26(6):784-791. doi: 10.1007/s12282-019-00988-x. Epub 2019 Jun 13.

Abstract

Background: Triple-negative breast cancer (TNBC), defined by lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), is characterized by early recurrence of disease and poor survival.

Objective: Here, we sought to identify genes associated with TNBC that could provide new insight into gene dysregulation in TNBC and, at the same time, provide additional potential therapeutic targets for breast cancer treatment.

Methods: Gene expression profiles from accession series GSE76275 were downloaded from the Gene Expression Omnibus database (GEO). The Cancer Genome Atlas (TCGA) was used to validate potential hub genes in the TCGA database. Protein-protein interaction (PPI) networks were identified using STRING (Search Tool for the Retrieval of Interacting Genes/Proteins). Finally, overall survival (OS) and relapse-free survival (RFS) analysis of hub genes was performed using a Kaplan-Meier plotter online tool.

Results: A total of 750 genes were identified after analysis of GSE76275. After validation with the TCGA database, a total of 155 differentially expressed genes (DEGs) were consistent with those identified by GSE76275. Based on the STRING database, we constructed a PPI network using the DEGs obtained from GSE76275 datasets. Furthermore, in the prognostic analysis of the 155 DEGs, we found that there were 10 genes associated with OS and 33 genes associated with RFS. Combined with the degree scores from the PPI network, a total of ten genes with the highest degree scores were selected as hub genes pertaining to TNBC.

Conclusion: Our research provides new insight into the subnetwork of biomarkers connected with TNBC, which could be useful for prognostication and risk stratification of TNBC patients.

Keywords: Differentially expressed genes; Interaction; Kaplan–Meier plotter; Protein–protein; Triple-negative breast cancer.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Computational Biology / methods*
  • Databases, Genetic
  • Disease-Free Survival
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Prognosis
  • Protein Interaction Maps / genetics
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Transcriptome*
  • Triple Negative Breast Neoplasms / genetics*
  • Up-Regulation / genetics

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2