Microarray Analysis for Differentially Expressed Genes Between Stromal and Epithelial Cells in Development and Metastasis of Invasive Breast Cancer

J Comput Biol. 2020 Dec;27(12):1631-1643. doi: 10.1089/cmb.2019.0154. Epub 2020 May 19.

Abstract

Both epithelium and stroma are involved in breast cancer invasion and metastasis. This study aimed at identifying the roles of the stroma in breast cancer tumorigenesis and metastasis. Gene expression profiling GSE10797 was downloaded from the Gene Expression Omnibus database, and it included 28-paired stroma and epithelium breast tissue samples from invasive breast cancer patients and 10 paired normal breast tissue samples. Differentially expressed genes (DEGs) between breast cancer and normal breast tissue samples were identified by using the limma package followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to seek the potential functions of DEGs. Moreover, a protein-protein interaction network was constructed based on the String database, and modules were selected through the BioNet tool. Further, functional annotations of DEGs were carried out by using tumor suppressor gene and tumor associated gene databases. Ultimately, KEGG pathway enrichment analysis for DEGs in modules was performed. A total of 38 and 156 DEGs were identified from normal invasive stromal cells and epithelial cells, respectively. DEGs in stromal and epithelial cells were significantly enriched in extracellular matrix (ECM)- and cell proliferation-related functions. COL1A2, a hub node in the stromal module, was mainly enriched in ECM-receptor interaction and focal adhesion pathways. JUN, a hub node in the epithelium module, was significantly enriched in cancer and ErbB signaling pathways. COL1A2, COL1A1, COL3A1, JUN, and FN1 might be vital for tumorigenesis and metastasis of invasive breast cancer. These genes might be potential therapeutic targets for breast cancer treatment.

Keywords: invasive breast cancer; module; protein–protein interaction network; stroma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Epithelial Cells / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Ontology
  • Gene Regulatory Networks
  • Humans
  • Oligonucleotide Array Sequence Analysis / methods*
  • Protein Interaction Maps / genetics
  • Stromal Cells / pathology