Integrative Bioinformatics Analysis of Breast Cancer-Derived Extracellular Vesicles in Mediating Cancer-Associated Fibroblast Activation

Breast cancer, the most frequently diagnosed cancer and the second leading cause of cancerrelatedmortality in women, is strongly influenced by the tumor microenvironment (TME). Extracellularvesicles (EVs) secreted by cancer cells within the TME play a pivotal role in inducing various effectsthrough diverse factors. Cancer-associated fibroblasts (CAFs) within the TME, activated by absorbingthese EVs, contribute to the development of a malignant phenotype in breast cancer [۱], [۲]. Activationof CAFs is associated with the Akt pathway and its upstream regulators [۳].The RNA-seq data (accession code GSE۱۰۶۵۰۳) sourced from the NCBI database focuses on CAFstreated with EVs from the MDA-MB-۲۳۱ cell line and CAFs treated with PBS. Data quality wasassessed using FastQC, and trim were made with the Trimmoamtic tool. HISAT۲ facilitated datamapping and alignment, with HTSeq-count analysis. Enrichr and the KEGG pathway database wereused to explore pathways associated with upregulated genes, and STRING was used to examine proteinproteininteraction networks.The study aims to investigate the impact of breast cancer-derived EVs on CAFs and understand theunderlying mechanisms. Among the upregulated genes influenced by EVs, ITGA۱۱, ITGB۵, THBS,and LAMB۱ are implicated in the upstream regulation of AKT and PI۳K pathways. Furthermore, ashared protein-protein interaction network involves ITGA۱۱, ITGB۵, THBS, LAMB۱, COL۱A۱,COL۵A۱, COL۶A۳, and POSTN genes.Considering the protein-protein interaction network among ITGA۱۱, ITGB۵, THBS, and LAMB۱, andtheir role in activating AKT and PI۳K signaling pathways, the increased expression of these genes dueto breast cancer-derived EVs may significantly contribute to promoting breast cancer malignancy withinthe TME.

کلیدواژه ها:

Breast cancer ، cancer associated fibroblast ، tumor microenvironment ، Extracellular vesicles