Investigation of the Genomic and Transcriptomic Variations Underlying Tamoxifen Resistance in Breast Cancer

Background: Breast cancer is a global burden responsible for millions of deaths per year. One of the significant challenges in the treatment of it is due to the emergence of resistance towards certain drugs, including well-known medication, Tamoxifen. With recent advances in technology, many genes have been identified to be involved in the progression of breast cancer and the development of resistance. Studying these genes and their potential pathways in cancer is a vital aspect of treatment that can enhance patients' response to therapeutic agents. Methods: In the present study, we investigated major genes associated with the risk of breast cancer and the creation of tamoxifen drug resistance within them. We analyzed data from GO datasets (GSE231629, GSE241654, and GSE42568). Differentially expressed genes were studied in the limma package in the R language and TAC software. Enrichr carried out gene ontology, gene set enrichment, and genomic pathway analysis. Gephi, Cytoscape, and STRING databases were employed to build the network of protein-protein interactions and miRNA-lncRNA-mRNA network. Results: analysis of differentially expressed genes demonstrated several hub genes including POSTN, COL1A2, LUM, COL3A1, BRINP3, TBX2-AS1, ARHGAP36, DSCAM-AS1 and SOX2 involved in breast cancer progression and resistance toward tamoxifen drug in MCF7 cell lines. These genes are associated with various biological processes such as intracellular signal transduction, MAPK Cas cade, gene expression, protein phosphorylation, and regulation of cell population proliferation. Conclusion: Our study demonstrates protein-protein interaction and significant genes involved in the development of breast cancer and tamoxifen resistance in MCF7 cell lines.