CHARACTERIZING THE MOLECULAR MECHANISM OF BREAST CANCER METASTASIS TO THE OVARIES

Abstract

Breast cancer continues to be a predominant cause of cancer-related death in women globally, with metastasis to distant organs substantially deteriorating patient prognosis. The ovaries constitute a distinctive metastatic location owing to their specific hormonal milieu, immunological interactions, and extracellular matrix composition. This work seeks to clarify the molecular pathways that regulate breast cancer metastasis to the ovaries by integrating transcriptome and proteomic analysis. Analysis of differential gene expression in ovarian cancer (GSE262869) and breast cancer (GSE31192) datasets revealed 2,393 and 1,013 differentially expressed genes (DEGs), respectively. STRING and Cytoscape analysis of 36 overlapping differentially expressed genes (DEGs) identified seven hub genes (EZH2, GZMB, NSD2, TPX2, GNAI1, SYK, and LCK), all of which were highly elevated in both malignancies. Gene ontology and KEGG pathway enrichment analysis revealed substantial participation in the PI3K/AKT/mTOR, MAPK, Wnt/β-catenin, and TGF-β signalling pathways, which govern tumour survival, invasion, and immune evasion. Epithelial-mesenchymal transition (EMT) was recognised as a primary catalyst for metastatic progression, mediated by transcription factors including Snail, Slug, Twist, and ZEB1/ZEB2. The ovarian tumour microenvironment, which is characterised by an abundance of hormones and cancer-associated fibroblasts, facilitates metastatic colonisation by promoting immune suppression and tumour development. The study emphasised the role of exosomes and microRNAs (miR-21, miR-200, and miR-10b) in influencing epithelial-mesenchymal transition (EMT) and drug resistance. A survival study using TCGA datasets revealed a significant association between the overexpression of EZH2, GZMB, NSD2, TPX2, and GNAI1 with worse patient prognosis, indicating their potential as prognostic biomarkers and therapeutic targets. Moreover, metabolic changes, including enhanced glycolysis and fatty acid oxidation, were identified in metastatic breast cancer cells, suggesting potential metabolic weaknesses for targeted treatment. This work emphasises the need for multiomics strategies to elucidate the intricacies of breast cancer metastasis to the ovaries. Identifying crucial regulatory genes and pathways provides a basis for developing tailored medicines and precision medicine tactics, eventually seeking to enhance early diagnosis, prognosis, and treatment results for patients with metastatic breast cancer.