Differential prognostic impact of interleukin-34 mRNA expression and infiltrating immune cell composition in intrinsic breast cancer subtypes

Abstract

Interleukin-34 (IL-34) is a ligand for the CSF-1R and has also two additional receptors, PTPRZ1 and syndecan-1. IL-34 plays a role in innate immunity, inflammation, and cancer. However, the role of IL-34 in breast cancer is still ill-defined. We analyzed IL-34 mRNA expression in breast cancer cell lines and breast cancer patients and applied established computational approaches (CIBERSORT, ESTIMATE, TIMER, TCIA), to analyze gene expression data from The Cancer Genome Atlas (TCGA). Expression of IL-34 was associated with a favorable prognosis in luminal and HER2 but not basal breast cancer patients. Gene expression of CSF-1 and CSF-1R was strongly associated with myeloid cell infiltration, while we found no or only weak correlations between IL-34, PTPRZ1, syndecan-1 and myeloid cells. In vitro experiments showed that tyrosine phosphorylation of CSF-1R, ERK, and FAK and cell migration are differentially regulated by IL-34 and CSF-1 in breast cancer cell lines. Collectively, our data suggest that correlation of IL-34 gene expression with survival is dependent on the molecular breast cancer subtype. Furthermore, IL-34 is not associated with myeloid cell infiltration and directly regulates breast cancer cell migration and signaling.