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Abstract
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Breast cancer is considered the main cancer in women and resistance to current
therapeutics is an increasing clinical challenge. So, it is essential to identify the
central genes and investigate the molecular mechanisms of resistant breast cancer
cells against tamoxifen. In the present study, microarray data related to resistant
breast cancer cells against tamoxifen as separately was analysed by R packages and
then combined analysis of all experiments was achieved by R packages in resistant
breast cancer cells against tamoxifen and then integrated p-values. Combine
analysis detected 437 down and 834 upregulated meta-DEGs (p-value cutoff < 0.
01). The DEGs were enriched in gene ontology terms related to cell death, response
to stress and chemical stimulus, and regulation of apoptotic processes. Based on
KEGG analysis, biological pathways including PI3K-Akt signaling pathway, Chemical
carcinogenesis, MAPK signaling pathway, and MicroRNAs in cancer were mainly
involved in tamoxifen resistance. The transcription factors (TFs) related to upregulated
genes mainly included ATF3, TFE3, C19orf25, TFCP, MAF, JUN, YY2, NKX3, FOS, and
SOX2 and downregulated genes such as ATF4, DDIT3, NFIL3, NFYA, E2Fs, TFDP3, and
SOX9. Generally, the hub upregulated genes mainly related to improving metastasis
of human cancer cells, oncogenic in cancer, proliferation of cells and apoptosis in
breast cancer. In addition, the hub downregulated genes mainly related to metastasis
process, drug resistance, and activation of endogenous DNA damage. Based on the
results from Spearman correlation and Logistic regression, the hub genes RECQL4
and ESPL1 as downregulated genes and CD59, ARCN1, and SAR1B as upregulated
genes play a prominent role in inducing resistance to tamoxifen. Overall, these genes
and TFs may be potential targets to improve the efficacy of therapy in breast cancer
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