Date of Submission

8-2023

Document Type

Thesis

Degree Name

Master of Science in Cellular and Molecular Biology

Department

Biology and Environmental Sciences

Advisor

Eva Sapi, Ph.D.

Keywords

Biomarkers, Borrelia burgdorferi, Breast Cancer, TNBC

MeSH

Biomarkers, Borrelia burgdorferi, Breast Neoplasms

LCSH

Biochemical markers, Borrelia burgdorferi, Breast--Cancer--Research

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options and a poor prognosis. Although some studies have attempted to identify new biomarkers and therapies, only a few have shown promise in clinical trials. In the context of cancer development, infectious agents rank as the third major risk factor, contributing to approximately 15-20% of cancer cases, according to the American Cancer Society. Hence, the identification of biomarkers associated with infection-originated cancer is crucial for enhancing cancer prevention, early detection, diagnosis, and treatment. Borrelia burgdorferi, the causative agent of Lyme disease, has been linked to TNBC and its aggressive characteristics. Therefore, investigating prognostic or diagnostic markers in B. burgdorferi-infected TNBC cells holds great potential for shedding light on the mechanisms underlying this complex association. In this study, we employed RNA-Sequencing (RNA-Seq) technology to examine changes in gene expression induced by B. burgdorferi infection in TNBC cell line MDA-MB-231 and a normal breast epithelial cell line (MCF10A). Our analysis identified common biomarkers, including CXCL-1, CXCL-8, C3, PTGS2 (COX2), and SAA1, in B. burgdorferi -infected TNBC cells. The genes identified for MCF10A included members of the CXCL family (CXCL10, CXCL8, CXCL3, and CXCL2), CCL20, and IFIT1. Furthermore, pathway analysis using KEGG and REACTOME databases revealed the involvement of the IL-4, 10, 13 & 17 signaling, TNF, NOD like receptor, TLR, NF-kB and Chemokine-signaling pathways. The most enriched signaling pathways in MCF10A included the IL-10 & 17, chemokine, cytokine and TNF signaling pathways. Common infectious diseases pathway associated in TNBC cells included COVID-19, Legionellosis, Prion disease, Influenza-A, Pertussis, Measles, Kaposi-sarcoma-associated herpesvirus, and Chagas disease, among others with several of the above identified genes in 7 function. The most common infectious disease associated pathways in MCF10A cells included Amoebiasis, Legionellosis, Hepatitis-C and Influenza-A. There were common metabolic pathways observed for MCF10A from the KEGG and REACTOME servers which include fatty acid metabolism, glycolipid metabolism and steroid metabolism. Also, certain biosynthesis pathways such as steroid and terpenoid backbone biosynthesis pathways were observed common from the KEGG and REACTOME servers for MCF10A.These findings highlight the significance of exploring these potential biomarkers as therapeutic targets in B. burgdorferi -associated TNBC. Our study provides a promising starting point for future research endeavors aimed at improving diagnostic and treatment strategies for this challenging infection-associated cancer subtype.

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