Novel Markers for Disease Outcome in Breast Cancer

Project 1 investigated proteomic, transcriptomic, and genomic effects of multilevel chronic stressors (perceived stress, social support, discrimination, neighborhood deprivation) in 121 African American and European American women with breast cancer. It involved patient surveys, collection of tumor and blood samples, and analysis of stress-related factors on immune-inflammation markers and tumor characteristics. Findings indicated chronic stressor-induced inflammation and immune dysfunction are associated with increased breast cancer aggressiveness and disparities, especially in African American women. Project 2 employed single-nucleus ATAC- and RNA-sequencing of 82 frozen breast tumors from African American, Kenyan, and European American women to characterize chromatin accessibility and gene expression patterns at single-cell resolution in relation to genetic ancestry, risk factors, and survival. A new protocol for isolating single nuclei from archival tissue was established, and a new analytic pipeline for Multiome sequencing data was developed. The project identified distinct pro-tumorigenic and immune-suppressive microenvironment characteristics in women of African descent predictive of survival.