Cancer Stem Cell Transcriptome Landscape Reveals Biomarkers Driving Breast Cancer Heterogeneity

Abstract

BackgroundBreast cancers are heterogeneous diseases with distinct clinical outcomes and cancer stem cell percentages. Exploring breast cancer stem cell landscape could help understand the heterogeneity of such cancers with profound clinical relevance.MethodsWe conducted transcriptional profiling of cancer stem cells and non-cancer stem cells isolated from 3 triple negative breast cancer cell lines, analyzed the cancer stem cell transcriptome landscape that drives breast cancer heterogeneity through differential expressed gene analysis, gene ontology and pathway enrichment as well as network construction, and performed experimental validations on the network hub gene.ResultsWe identified a cancer stem cell feature panel consisting of 122 and 381 over-represented and under-expressed genes capable of differentiating breast cancer subtypes. We also underpin the prominent roles of the PI3K-AKT pathway in empowering cancer cells with uncontrolled proliferative and migrative abilities that ultimately foster cancer stemness, and reveal the potential promotive roles of ATP6V1B1 on breast tumor stemness through functional in vitro studies. ConclusionsOur study contributes in identifying a cancer stem cell feature panel for breast tumors that drives breast cancer heterogeneity at the transcriptional level, which provides a reservoir for diagnostic marker and/or therapeutic target identification once experimentally validated as demonstrated by ATP6V1B1.