Abstract P6-13-01: EPITHELIAL-MESENCHYMAL TRANSITION AND TUMOR STEM CELLS NETWORK IDENTIFICATION IN BREAST CARCINOMAS: IN SILICO STUDY

Abstract

Abstract INTRODUCTION: Breast cancer (BC) is the most prevalent malignant tumor in the female population, except for skin tumors. Despite therapeutic advances, over 20% of patients with localized disease will relapse. The research of epithelial-mesenchymal transition (EMT), tumor stem cells (TSC), and the biological mechanisms related to refractoriness and metastasis development is, therefore, an opportunity for new therapeutic strategies and better results. OBJECTIVES: To identify breast cancer cellular markers related to EMT and TSC according to their histological subtypes, stage and to analyze their relationship with clinical outcomes. METHODS: After selecting a public breast cancer patients database with interactome, we identified differentially expressed genes, their associated processes, coexpression networks and interactions with pathways related to the stem phenotype and epithelial-mesenchymal transition. The characterization of key genes and the correlation with histological subtypes and clinical outcome allowed us to determine a group of genes as potential breast cancer EMT/TSC prognostic markers. RESULTS: In the 989 patients studied, 1033 differentially expressed genes (DEGs) were found, categorized according to histological subtype (hormone receptor positive, HER2 positive, triple negative) and stage IV. Seven communities of gene coexpression were found, with the gray community showing greater interaction with hormone positive tumors, the green community with HER2 positive, and the turquoise community with the triple negative one. The hormone positive disease was related to extracellular matrix processes and neuronal communication, the HER2 positive to the extracellular matrix interaction and the triple negative tumors to mitotic processes. Investigation networks with EMT and TSC related genes demonstrated a strong correlation with HER2-positive and triple-negative tumors; being eight genes in HER2 positive subtypes correlated with survival (SYNDIG1, ​​COL10A1, SLC24A2, LINC00922, KLKP1, MMP11 and ECM2); and one of the hormone positive subtype (ITIH5). ECM2 was highlighted in terms of EMT/TSC connectivity and survival. CONCLUSION:The EMT/TSC processes are significant in the various subtypes of breast cancer and impact on survival, especially in the HER2 positive subtype. Citation Format: Vanessa Dybal, Bruno R. Cavalcante, Gisele V. Rocha, Clarissa Gurgel. EPITHELIAL-MESENCHYMAL TRANSITION AND TUMOR STEM CELLS NETWORK IDENTIFICATION IN BREAST CARCINOMAS: IN SILICO STUDY. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-13-01.