The role of gene to gene interaction in the breast's genomic signature of pregnancy

Sci Rep. 2021 Jan 29;11(1):2643. doi: 10.1038/s41598-021-81704-8.

Abstract

Full-term pregnancy at an early age confers long-term protection against breast cancer. Published data shows a specific transcriptomic profile controlling chromatin remodeling that could play a relevant role in the pregnancy-induced protection. This process of chromatin remodeling, induced by the breast differentiation caused by the first full-term pregnancy, has mainly been measured by the expression level of genes individually considered. However, genes equally expressed during the process of chromatin remodeling may behave differently in their interaction with other genes. These changes at the gene cluster level could constitute an additional dimension of chromatin remodeling and therefore of the pregnancy-induced protection. In this research, we apply Information and Graph Theories, Differential Co-expression Network Analysis, and Multiple Regression Analysis, specially designed to examine structural and informational aspects of data sets, to analyze this question. Our findings demonstrate that, independently of the changes in the gene expression at the individual level, there are significant changes in gene-gene interactions and gene cluster behaviors. These changes indicate that the parous breast, through the process of early full-term pregnancy, generates more modules in the networks, with higher density, and a genomic structure performing additional and more complex functions than those found in the nulliparous breast.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Differentiation / genetics
  • Epistasis, Genetic / genetics*
  • Epithelial Cells / metabolism
  • Female
  • Gene Expression Regulation / genetics
  • Genome, Human / genetics
  • Genomics*
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Postmenopause / genetics
  • Pregnancy
  • Transcriptome / genetics*