Multi-omics integration analysis unveils heterogeneity in breast cancer at the individual level

Identifying robust breast cancer subtypes will help to reveal the cancer heterogeneity. However, previous breast cancer subtypes were based on population-level quantitative gene expression, which is affected by batch effects and cannot be applied to individuals. We detected differential gene expression, genomic, and epigenomic alterations to identify driver differential expression at the individual level. The individual driver differential expression reflected the breast cancer patients' heterogeneity and revealed four subtypes. Mesenchymal subtype as the most aggressive subtype harbored deletion and downregulated expression of genes in chromosome 11q23 region. Specifically, silencing of the SDHD gene in 11q23 promoted the invasion and migration of breast cancer cells in vitro by the epithelial-mesenchymal transition. The immunologically hot subtype displayed an immune-hot microenvironment, including high T-cell infiltration and upregulated PD-1 and CTLA4. Luminal and genomic-unstable subtypes showed opposite macrophage polarization, which may be regulated by the ligand-receptor pairs of CD99. The integration of multi-omics data at the individual level provides a powerful framework for elucidating the heterogeneity of breast cancer.