Potential Molecular Crosstalk Between Breast Cancer Cells and Peripheral Immune System Based on Integrative Omics Strategy

Objective To investigate the molecular crosstalk between breast tumor tissues and peripheral blood mononuclear cells (PBMCs).

Methods Two publicly available microarray datasets of breast tumor epithelium and PBMCs respectively were analyzed by bioinformatics approaches. Differentially expressed genes were identified by GEO2R online analysis tools. Then protein-protein interactions (PPIs), protein subcellular localization information from UniProt and STRING database were integrated to identify the genes that contribute to the dialogue. Function and pathways of that involved in the dialogue between the tumor cells and the peripheral circulation were annotated by the Database for Annotation, Visualization and Integrated Discovery (DAVID).

Results A total of 101 interaction relationships were identified and visualized. Function and pathway analysis indicated that biology processes included cell adhesion, regulation of cell motion, leukocyte activation, and immune response. And the crossstalk molecules were enriched in ECM-receptor interaction, cytokine-cytokine receptor interaction, and chemokine signaling pathway. The genes such as FN1, ITGB1, FLT1, CXCR3, COPM, CXCL12 were the hub nodes of the crosstalk network and may play an important role in the response for tumor-derived chemoattractants.

Conclusion Bioinformatic tools can extract the effective information through integrative analysis of multi-omics data. This study has the potential for development of new therapeutic and the prognosis monitoring strategies against breast cancer.