Heterocellular gene signatures reveal luminal-A breast cancer heterogeneity and differential therapeutic responses.
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Embargo End Date
ICR Authors
Authors
Poudel, P
Nyamundanda, G
Patil, Y
Cheang, MCU
Sadanandam, A
Nyamundanda, G
Patil, Y
Cheang, MCU
Sadanandam, A
Document Type
Journal Article
Date
2019-08-02
Date Accepted
2019-06-25
Abstract
Breast cancer is a highly heterogeneous disease. Although differences between intrinsic breast cancer subtypes have been well studied, heterogeneity within each subtype, especially luminal-A cancers, requires further interrogation to personalize disease management. Here, we applied well-characterized and cancer-associated heterocellular signatures representing stem, mesenchymal, stromal, immune, and epithelial cell types to breast cancer. This analysis stratified the luminal-A breast cancer samples into five subtypes with a majority of them enriched for a subtype (stem-like) that has increased stem and stromal cell gene signatures, representing potential luminal progenitor origin. The enrichment of immune checkpoint genes and other immune cell types in two (including stem-like) of the five heterocellular subtypes of luminal-A tumors suggest their potential response to immunotherapy. These immune-enriched subtypes of luminal-A tumors (containing only estrogen receptor positive samples) showed good or intermediate prognosis along with the two other differentiated subtypes as assessed using recurrence-free and distant metastasis-free patient survival outcomes. On the other hand, a partially differentiated subtype of luminal-A breast cancer with transit-amplifying colon-crypt characteristics showed poor prognosis. Furthermore, published luminal-A subtypes associated with specific somatic copy number alterations and mutations shared similar cellular and mutational characteristics to colorectal cancer subtypes where the heterocellular signatures were derived. These heterocellular subtypes reveal transcriptome and cell-type based heterogeneity of luminal-A and other breast cancer subtypes that may be useful for additional understanding of the cancer type and potential patient stratification and personalized medicine.
Citation
NPJ breast cancer, 2019, 5 pp. 21 - ?
Source Title
Publisher
NATURE PORTFOLIO
ISSN
2374-4677
eISSN
2374-4677
Collections
Research Team
Genomic Analysis – Clinical Trials
Systems and Precision Cancer Medicine
Systems and Precision Cancer Medicine