Evaluation of molecular pathways associated with breast cancer disparities

In this dissertation, an integrated approach of metabolomics, proteomics, and validation studies in vitro, were combined to evaluate molecular pathways associated with breast cancer disparities. The chapters on this dissertation explore the role of biological mechanisms altered in patients from diverse racial backgrounds with estrogen receptor positive breast cancer. We have used multiple tools to explore various factors that have molecular effects and in turn impact breast cancer disparities. In the first part of this thesis, we focused on synthesizing several mechanisms that have been proposed to be altered in African American patients with estrogen receptor positive breast cancer. Our second chapter emphasizes the disparities in exposure to endocrine disruptors among racial and ethnic groups and the lack of inclusion of socially disadvantage populations in breast cancer research. We highlight the association of endocrine disruptors exposure with breast cancer, and the importance of understanding this relationship to mitigate exposures and improved breast cancer disparities. On a separate chapter, we focused on the association of plasma levels of endocrine disruptor and proteins related to inflammation in menopausal women and breast cancer patients and a susceptible cohort of patients. Our findings suggested that exposure to PFAS is linked to altered proteomics profile in menopausal women. We then focused on identifying potential circulating biomarkers for breast cancer risk using metabolomics and proteomics analysis of blood samples. We used various statistical and machine learning methods to identify molecules with predictive power. These biomarkers could be used in the development of low-cost liquid biopsy methods for early diagnosis. Next, in chapter 4, using advanced statistical and machine learning techniques we identified differential metabolic signatures and associated them with specific regulatory mechanisms. These findings provided insights into the aggressive tumor biology in African American women and may contribute to the identification of novel therapeutic targets. We then examined and validated findings from chapter 4 by invitro settings and clinical data from The Cancer Genome Atlas program (TCGA). Our findings revealed higher levels of SLC25A1 mRNA (transporter responsible for citrate export) in African American patients compared to Non-Hispanic White patients. In vitro experiments demonstrated that extracellular citrate increases cell proliferation and migration in ER+ cell lines, primary in AA cell lines, and affects the gene expression of mitochondrial and cytosolic enzymatic programs. The study identified SLC25A1 as a potential aggressiveness marker and highlights its role in regulating mitochondrial and cytosolic enzymatic programs in AA cell lines. These chapters shed light on the racial disparities in breast cancer outcomes and the role of metabolic alterations on aggressive tumor biology. By synthesizing recent findings these chapters contribute to our knowledge on breast cancer and provide multifaceted insights into addressing health disparities and improving patients’ outcomes. Collectively, these studies contribute to the body of knowledge surrounding breast cancer and serve as a foundation for future research and interventions aimed at reducing mortality rates and improving outcomes for all individuals affected by this disease.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Nutritional Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2023

Author dc:creator

• Santaliz Casiano, Ashlie M

Contributors dc:contributor

• Madak-Erdogan, Zeynep
• Gaskins, Rex
• Spinella, Michael
• Arthur, Anna

• Breast Cancer
• Cancer Disparities
• Metabolomics
• Proliferation
• Exposures

Statement dc:rights

• Copyright 2023 Ashlie Santaliz Casiano

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/122247

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F122247