Interactions between the tumor and the blood systemic response of breast cancer patients

PLoS Comput Biol. 2017 Sep 28;13(9):e1005680. doi: 10.1371/journal.pcbi.1005680. eCollection 2017 Sep.

Abstract

Although systemic immunity is critical to the process of tumor rejection, cancer research has largely focused on immune cells in the tumor microenvironment. To understand molecular changes in the patient systemic response (SR) to the presence of BC, we profiled RNA in blood and matched tumor from 173 patients. We designed a system (MIxT, Matched Interactions Across Tissues) to systematically explore and link molecular processes expressed in each tissue. MIxT confirmed that processes active in the patient SR are especially relevant to BC immunogenicity. The nature of interactions across tissues (i.e. which biological processes are associated and their patterns of expression) varies highly with tumor subtype. For example, aspects of the immune SR are underexpressed proportionally to the level of expression of defined molecular processes specific to basal tumors. The catalog of subtype-specific interactions across tissues from BC patients provides promising new ways to tackle or monitor the disease by exploiting the patient SR.

MeSH terms

  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Blood Cells / physiology*
  • Breast Neoplasms / physiopathology*
  • Case-Control Studies
  • Cellular Microenvironment / physiology*
  • Female
  • Gene Expression Profiling
  • Genomics
  • Humans
  • Middle Aged
  • Signal Transduction
  • Systems Biology
  • Tumor Microenvironment / physiology*

Substances

  • Biomarkers, Tumor

Grants and funding

We acknowledge funding from the European Research Council (ERC-2008-AdG-232997); the Canadian Cancer Society Research Institute (INNOV2-2014-702940). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.