Abstract B50: The role of CXCL13-CXCR5 signaling in triple-negative breast cancer progression

Triple-negative breast cancer (TNBC) is an aggressive cancer with poor prognosis and is difficult to treat. There is a major health disparity associated with TNBC; the number of fatalities associated with this disease is significantly higher in African American women compared to their Caucasian counterparts. The mechanisms behind these differences have not been entirely elucidated. There are no targeted therapies for TNBC; instead, standard therapy for this disease includes a combination of chemotherapeutic drugs: doxorubicin (DOX), paclitaxel (TAX), and/or cyclophosphamide (CTX). Even more troubling, the efficacy of standard TNBC therapies is marginal and patients eventually become resistant to this intervention. TNBC patients suffer from chemoresistance and metastasis and ultimately succumb to this disease. Understanding TNBC and its health disparity requires a better understanding of the race-specific differences in breast tumor biology, molecules leading to breast inflammation, and the mechanisms associated with TNBC chemoresistance. Chemokines and their receptors play a significant role in TNBC. Our laboratory was the first to show that CXCL13-CXCR5 signaling mediates prostate cancer cell growth, migration, invasion, and survival (1-3). We also demonstrated that CXCL13-CXCR5 signaling induces cancer progression signaling pathways PI3K, AKT, ERK, and Jun (1;4). These preliminary and published findings provide the rationale or scientific premise in support of our hypothesis that CXCL13-CXCR5 signaling promotes TNBC progression migration, invasion, proliferation, and chemoresistance. To determine whether CXCL13-CXCR5 signaling induces TNBC, the expression profile of CXCL13 and CXCR5 RNA, associated miRNAs, and cancer progression genes (epithelial mesenchymal transition [EMT] markers) will be correlated with disease-free and overall survival of TNBC patients in silico using RNA-seq datasets from the Sequence Read Archive (SRA). Fastq data set files were downloaded from SRA, checked for quality control, aligned, and normalized using open-source platforms. Hierarchical clustering, gene set enrichment analysis, disease progression analysis, and statistics were conducted using Partek Genomic Suite. Pathway enrichment analysis was conducted using Ingenuity Pathway Studios. Overall, CXCL13-CXCR5 signaling is implicated in TNBC progression, migration, and invasion. Citation Format: Courtney D. Dill, Adaugo Okoro, Dongquan Chen, James W. Lillard, Jr.. The role of CXCL13-CXCR5 signaling in triple-negative breast cancer progression [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B50.