Abstract
The present study aimed to identify the differentially expressed genes (DEGs) and enriched pathways in docetaxel (DTX) resistant breast cancer cell lines by bioinformatics analysis. The microarray dataset GSE28784 was obtained from gene expression omnibus (GEO) database. The differentially expressed genes (DEGs), gene ontology (GO), and Kyoto Encyclopedia of gene and genome (KEGG) pathway analyses were performed with the help of GEO2R and DAVID tools. Furthermore, the protein–protein interaction (PPI) and hub-gene network of DEGs were constructed using STRING and Cytohubba tools. The prognostic values of hub genes were calculated with the help of the Kaplan–Meier plotter database. From the GEO2R analysis, 222 DEGs were identified of which 120 are upregulated and 102 are downregulated genes. In the PPIs network, five up-regulated genes including CCL2, SPARC, CYR61, F3, and MFGE8 were identified as hub genes. It was observed that low expression of six hub genes CXCL8, CYR61, F3, ICAM1, PLAT, and THBD were significantly correlated with poor overall survival of BC patients in survival analysis. miRNA analysis identified that hsa-mir-16-5p, hsa-mir-335-5p, hsa-mir-124-3p, hsa-mir-20a-5p, and hsa-mir-155-5p are the top 5 interactive miRNAs that are commonly interacting with more hub genes with degree score of greater than five. Additionally, drug-gene interaction analysis was performed to identify drugs which are could potentially elevate/lower the expression levels of hub genes. In summary, the gene-miRNAs-TFs network and subsequent correlation of candidate drugs with hub genes may improve individualized diagnosis and help select appropriate combination therapy for DTX-resistant BC in the future.
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Acknowledgements
Baddipadige Raju and Gera Narendra would like to acknowledge the Indian Council of Medical Research (ICMR), New Delhi for providing a Senior Research Fellowship (SRF).
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This work was supported by the Indian Council of Medical Research (ICMR), New Delhi; Sanction No. ISRM/12(10)/2019.
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Baddipadige Raju: Concept, Designing of Work, Original Manuscript Writing, Editing, Software usage, Analysis, and Interpretation of Data. Gera Narendra: Designing of work, Software usage, and Data interpretation. Himanshu Verma: Data interpretation, Manuscript Editing. Om Silakari: Designing of work, Editing, and Proofreading.
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Raju, B., Narendra, G., Verma, H. et al. Identification of chemoresistance associated key genes-miRNAs-TFs in docetaxel resistant breast cancer by bioinformatics analysis. 3 Biotech 14, 128 (2024). https://doi.org/10.1007/s13205-024-03971-2
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DOI: https://doi.org/10.1007/s13205-024-03971-2