Cancer stem cell transcriptome landscape reveals biomarkers driving breast carcinoma heterogeneity

• Published in: Breast cancer research and treatment Vol. 186; no. 1; pp. 89 - 98
• Main Authors: Zhang, Zhifa, Chen, Xiao, Zhang, Jianying, Dai, Xiaofeng
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-02-2021; Springer; Springer Nature B.V
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Breast cancer; Breast carcinoma; Cancer; Cancer research; Carcinoma; Gene expression; Genetic aspects; Medical colleges; Medicine; Medicine & Public Health; Oncology; Preclinical Study; Stem cells; Therapeutic targets; Transcription; Transcriptomes; Tumor cell lines; Cancer stem cell; Breast carcinoma; Biomarker; Transcriptome
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-020-06045-y

Background
Breast carcinomas are heterogeneous diseases with distinct clinical outcomes and cancer stem cell (CSC) percentages. Exploring breast carcinoma stem cell landscape could help understand the heterogeneity of such cancers with profound clinical relevance.
Methods
We conducted transcriptional profiling of CSCs and non-stem cancer cells isolated from three triple-negative breast carcinoma cell lines, analyzed the CSC transcriptome landscape that drives breast carcinoma heterogeneity through differentially expressed gene identification, gene ontology (GO) and pathway enrichment analyses as well as network construction, and experimentally validated the network hub gene.
Results
We identified a CSC feature panel consisting of 122 and 381 over-represented and under-expressed genes capable of differentiating breast carcinoma subtypes. We also underpinned the prominent roles of the PI3K-AKT pathway in empowering carcinoma cells with uncontrolled proliferative and migrative abilities that ultimately foster cancer stemness, and revealed the potential promotive roles of
ATP6V1B1
on breast carcinoma stemness through functional in vitro studies.
Conclusions
Our study contributes in identifying a CSC feature panel for breast carcinomas that drives breast carcinoma heterogeneity at the transcriptional level, which provides a reservoir for diagnostic marker and/or therapeutic target identification once experimentally validated as demonstrated by
ATP6V1B1
.