ABSTRACT
PURPOSE: Breast cancer (BRCA) is characterized by a unique metastatic pattern, often presenting with bone metastasis (BoM), posing significant clinical challenges. Through the study of the immune microenvironment in BRCA BoM offer perspectives for therapeutic interventions targeting this specific metastatic manifestation of BRCA. METHODS: This study employs single-cell RNA sequencing and TCGA data analysis to comprehensively compare primary tumors (PT), lymph node metastasis (LN), and BoM. RESULTS AND CONCLUSIONS: Our investigation identifies a metastatic niche in BoM marked by an increased abundance of cancer-associated fibroblasts (CAFs) and reduced immune cell presence. A distinct subtype (State 1) of BRCA BoM cells associated with adverse prognosis is identified. State 1, displaying heightened stemness traits, may represent an initiation phase for BoM in BRCA. Complex cell communications involving tumor, stromal, and immune cells are revealed. Interactions of FN1, SPP1, and MDK correlate with elevated immune cells in BoM. CD46, MDK, and PTN interactions drive myofibroblast activation and proliferation, contributing to tissue remodeling. Additionally, MDK, PTN, and FN1 interactions influence FAP+ CAF activation, impacting cell adhesion and migration in BoM. These insights deepen our understanding of the metastatic niche in breast cancer BoM.
ABSTRACT
In this paper, we present the use of Principal Component Analysis and customized software, to accelerate the spectral analysis of biological samples. The work is part of the mission of the National Institute of Environmental Health Sciences sponsored Puerto Rico Testsite for Exploring Contamination Threats Center, establishing linkages between environmental pollutants and preterm birth. This paper provides an overview of the data repository developed for the Center, and presents a use case analysis of biological sample data maintained in the database system.