Multiomic Analysis Links Neighborhood Disadvantage to Inflammatory Proteins and Tumorigenic Markers in ER+ Breast Cancer Plasma and Tumor Samples
Residing in disadvantaged neighborhoods has been linked to worsened survival among Black women with estrogen receptor-positive (ER+) breast cancer (BC), yet the underlying multiomic alterations remain underexplored. To investigate associations between neighborhood deprivation and pretreatment steroid hormones, untargeted metabolites, inflammatory proteins, and tumoral gene expression in women with primary ER+ BC and cancer-free controls, pretreatment plasma was collected from ER+ BC patients (<i>n</i> = 91) and controls (<i>n</i> = 141) across three Chicago hospitals. Area deprivation index (ADI) was calculated per participant. Plasma was analyzed via targeted steroid hormone and untargeted metabolomics assays, and Olink's inflammatory protein panel. Tumor samples (<i>n</i> = 71) were analyzed using the Nanostring Breast Cancer 360 panel. Single-omic analysis and multiomics integration were performed. Elevated inflammatory proteins were observed in cases and controls from disadvantaged neighborhoods (<i>p</i> < 0.05), and tumoral gene expression showed upregulation of inflammatory and proliferation-related genes (<i>p</i> < 0.05). Patients from deprived areas exhibited higher inflammation and antioxidant depletion even within the same tumor grade (<i>p</i> < 0.05). Neighborhood deprivation correlates with pro-inflammatory, proliferative multiomic profiles that may underlie worsened outcomes.
Authors
- Jonna Frasor (ORCID: https://orcid.org/0000-0002-6003-1867)
- Hannah McGee (ORCID: https://orcid.org/0000-0003-1417-993X)
- Garth H. Rauscher (ORCID: https://orcid.org/0000-0003-0374-944X)
- Oana C. Danciu (ORCID: https://orcid.org/0000-0003-4487-9136)
- Sarah M. Friedewald (ORCID: https://orcid.org/0000-0002-9623-7533)
- Elona Liko Hazizi
- Zeynep Madak‐Erdogan (ORCID: https://orcid.org/0000-0003-2607-1643)
- Natalie Pulliam
- Seema A. Khan (ORCID: https://orcid.org/0000-0002-6307-2023)
- Kent Hoskins (ORCID: https://orcid.org/0000-0001-8712-0299)
- J. Julie Kim
- William J. Gradishar (ORCID: https://orcid.org/0000-0002-2772-3140)
- Ashlie Santaliz Casiano (ORCID: https://orcid.org/0000-0002-8821-8009)
- Hannah Heath (ORCID: https://orcid.org/0000-0003-2569-4734)
- Margaret Wright Geise
- Ekas Abrol (ORCID: https://orcid.org/0009-0008-4933-0381)
- Ayesha Zaidi
- Farizi Fazli
Institutions
- Northwestern University (US)
- National Institutes of Health (US)
- University of Illinois Urbana-Champaign (US)
- University of Illinois System (US)
- University of Illinois Chicago (US)
- University of Chicago (US)
- Genesis Foundation (US)
- Palmetto Hematology Oncology (US)
- National Cancer Institute (US)
- Center for Cancer Research (US)
Publication Details
- Journal
- Journal of Proteome Research
- Published
- 2025-09-02
- DOI
- https://doi.org/10.1021/acs.jproteome.5c00447
- Primary Topic
- Ferroptosis and cancer prognosis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Northwestern University
- National Institutes of Health
- University of Illinois at Urbana-Champaign
- National Institute of Food and Agriculture
- Feinberg School of Medicine
- University of Illinois at Chicago
- National Cancer Institute
- College of Agricultural, Consumer and Environmental Sciences, University of Illinois at Urbana-Champaign
- Cancer Center, University of Illinois at Chicago