In many solid Notch pathway is deregulated, affecting most hallmarks in cancer. Notch pathway plays a key role in cellular differentiation and its dysregulations contributes to carcinogenesis. Notch gene expression is frequently altered in breast cancer (BC) and exists ample evidence of the role of Notch in tumor formation, progression and resistance to treatment in BC. A less explored function of Notch pathways in cancer is their role in leukocyte homing and activation. Understanding their role and relationship with immune infiltrates is an area of interest in cancer research.
The expression of four different Notch genes (Notch1, Notch2, Notch3 and Notch4) was explored in relation with A luminal BC patient outcome using transcriptomic data (Affymetrix dataset, exploratory cohort) and the METABRIC study (validation cohort). The TIMER online tool was used to explore the association of the identified notch and immune infiltration, and the TCGA and METABRIC studies to analyze the correlation between notch1 - 4 expression and genomic signatures of immune activation.
We identified 2 individual genes called Notch1 and Notch2, which predict favorable prognosis in luminal A breast cancer. Their expression positively correlated with the presence of immune infiltrates within the tumor (dendritic cells, CD4+ T cells, neutrophils, CD8+ T cells and B cells), with markers of T cell activation and antigen presentation, and with gene signatures of immune surveillance (cytotoxic T lymphocyte activation and IFN gamma signature). By contrast Notch3 and Notch4 which predicted for detrimental outcome were not associated with any of these parameters.
Our analysis identifies a Notch signature composed of 2 genes with potential to recognize immune infiltrated and activated A luminal phenotype BC with favorable prognosis.
The authors.
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All authors have declared no conflicts of interest.