Unravelling the biological characteristics of MammaPrint ultra-low risk group

Background MammaPrint^® (MP) is a 70-gene based assay that stratifies early-stage breast cancer (EBC) patients into low and high-risk of relapse. Further stratification of the MP risk results identified an Ultra-Low (UL) subgroup of early-stage hormone receptor positive breast cancer with a 20-year long-term survival rate of 94-97% (Delahaye et al, 2017, Esserman et al, 2017). In this study, we aim to gain more insight into the biology of UL subgroup using differentially expressed genes (DEGs) analysis.

Methods For DEG analysis, we selected full-transcriptome data from formalin-fixed paraffin-embedded (FFPE) samples available at Agendia. For the UL subgroup, we selected the 100 samples with the highest MP index. For the Low Risk (LR) subgroup, we selected the 100 samples with the lowest MP index in this group. Only BluePrint Luminal subtype was selected. The LR was compared to the UL risk group using Limma and subsequent pathway analysis with Gene Set Enrichment Analysis (GSEA).

Results Differential expression analysis between UL and LR revealed 48 genes, which are involved in activating invasion and metastatis, proliferation and angiogenesis: “epithelial_mesenchymal_transition”, “oxidative phosphorylation”, “angiogenesis” and “TGF_beta_signaling” were upregulated, while “G2M_checkpoint, hypoxia”, “proliferation”, “inflammatory response”, “avoiding immune destruction” and “TNFA_signaling_via_NFKB” were downregulated in UL vs. LR.

Conclusion In this study we show different biological characteristics of UL MP. Our results highlight underlying biological processes of extreme low risk MP samples, which might guide relevant treatment decisions concerning endocrine therapy of hormone receptor positive EBC.

Publication History

Article published online:
07 October 2020