Use of a Novel Embryonic Mammary Stem Cell Gene Signature to Improve Human Breast Cancer Diagnostics and Therapeutic Decision Making
Technical Report,30 Sep 2012,29 Sep 2015
University of North Carolina at Chapel Hill Chapel Hill United States
Pagination or Media Count:
Our major goals are to determine whether Fetal Mammary Stem Cell fMaSC signatures correlate with response to chemotherapy and metastasis in different breast cancer intrinsic subtypes AIM1, and to develop single cell sequencing to produce highly refined fMaSC signatures AIM2. Accomplishing these aims will enable us to 1 better categorize distinct cell types within the fMaSC population, 2 identify biomarkers for prospective stem cell purification and in situ localization, and 3 identify candidate stem cell regulatory pathways that should reveal therapeutic targets and improved prognosticators and response biomarkers. In the most recent funding period, our bioinformatic analysis identified subsets of fMaSC signature genes that are coordinately expressed in archived human breast cancer gene expression data sets and assessed their prognostic andor predictive power. We have thus far identified one subset exhibiting significant prognostic value distinct from existing and commonly used clinical variables in the preliminary data sets we have analyzed. We have also adapted a new microfluidics-based, single-cell capture and library preparation system to improve reproducibility in the generation of gene expression profiles from individual fMaSC. These advances provide proof of the principles underlying this grant and leave us well positioned to achieve its aims.