Systems biology approaches for the study of signaling pathways by RNA-seq in triple-negative breast cancer cell lines

Abstract

Breast carcinoma is the most frequently diagnosed type of cancer among women, with the ductal-invasive triple-negative being the most aggressive, displaying the worst prognosis. Due to the lack of molecular targets, the treatment of patients presenting this phenotype becomes a great challenge, requiring more extensive studies to better understand the biology of this tumor type for the development of new therapeutic strategies. These studies have been carried out by the NUCEL group of researchers in an attempt to nd new molecular targets of clinical interest. To this end, the CD90 stem cell marker was identied by Dr. Aline Maia Lobba as being a promising target in breast cancer, since it was associated with the poor prognosis of patients and with several cellular processes which lead to malignant transformation, such as: morphological alteration, epithelial-mesenchymal transition, increased cell proliferation, invasiveness, metastasis and activation of the EGFR pathway. More than 78% of triple-negative breast cancer cases show overexpression of EGFR, allowing us to study their components and attempt to identify a potential therapeutic target. Therefore, understanding of the CD90 signaling pathway and its possible relationship with the EGFR pathway should be an interesting approach towards the molecular basis of basal-like mammary tumorigenesis. Therefore, the central objective of this project is elucidation of the CD90 signaling pathway and its relationship to the EGFR pathway in regulation of the downstream gene expression process. This project is being developed through a multidisciplinary approach involving Systems Biology, combined with conventional technologies of Cellular and Molecular Biology for validation of the results obtained through mathematical and Bioinformatics analysis. There will be evaluated different methods to identify differentially expressed genes and approaches for pathway enrichment analysis, aiming the establishment of a new approach for the integration of these methods to elucidate the CD90 signaling pathway and its relation with the EGFR pathway in the regulation of gene expression and relation with other pathways and biological processes. The knowledge generated in this work should contribute not only to the understanding of the molecular mechanisms underlying the origin and progression of breast cancer, but, also, to pave the way for the development of new therapeutic strategies.