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pmid:34967576
Genomic Understanding Reveals the Important Role of FGFR2 as Paeoniflorin Target for Circumventing Breast Cancer Resistance to Tamoxifen.
Moh Arikus Wibowo · Eri Prasetyo Nugroho · Adam Hermawan
Asian Pacific journal of cancer prevention : APJCP · 2021 doi:10.31557/APJCP.2021.22.12.3949
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Complete file
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To date, the mechanism of overcoming tamoxifen resistance in breast cancer is not yet elucidated. This research aims to explore the potential target of PF as a co-treatment for circumventing breast cancer resistance to tamoxifen with a genomic understanding-bioinformatics.\nMETHODS: Microarray data originating from GSE67916 and GSE85871 in the NCBI GEO database was analyzed to obtain differentially expressed genes (DEGs). Further analyses were performed on DEGs using the DAVID v6.8, STRING-DB v11.0, the Cytoscape, and cBioportal. Gene expression analysis validation in breast cancer cells and tamoxifen-resistant breast cancer cells was accomplished using GEPIA and ONCOMINE databases. Survival rate analysis of selected genes was conducted using Kaplan-Meier.\nRESULTS: We obtained 175 DEGs from the two samples (tamoxifen-resistant and paeoniflorin-treated). DEG involves in 70 biological processes, 26 cellular components, and 18 molecular functions, and three pathways relevant to breast cancer. The PPI network analysis and hub genes selection obtained 10 genes with the highest degree scores. Genetic changes for selected genes, including IFNB1, CDK6, FGFR2, OAS1, BCL2, and STAT2 were found from 0.5% to 7% of the case population per patient case. Additional analysis using cBioportal revealed FGFR signaling pathway through Ras is important for the PF mechanism in circumventing breast cancer resistance to tamoxifen. ONCOMINE and GEPIA analysis emphasized the importance of selected genes in the tamoxifen-resistance mechanism.\nCONCLUSION: PF has potential to be used as a co-treatment for circumventing breast cancer resistance to tamoxifen by targeting FGFR2 signaling, but further validation is needed.", "claims": [{"id": "claim-method", "statement": "The microarray data of the two GSE codes were further analyzed using the GEO2R to identify differentially expressed genes (DEGs) (Zhang et al., 2020).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34967576", "locator": "sections[2] \"Materials and Methods\" paragraph 3", "quote": "The microarray data of the two GSE codes were further analyzed using the GEO2R to identify differentially expressed genes (DEGs) (Zhang et al., 2020)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are available in the supplementary files and available in http://ugm.id/PFRTA", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34967576", "locator": "sections[7] \"Availability of data\" paragraph 2", "quote": "The data that support the findings of this study are available in the supplementary files and available in http://ugm.id/PFRTA"}], "state": "complete"}, {"id": "claim-target-result", "statement": "We obtained 175 DEGs from the two samples (tamoxifen-resistant and paeoniflorin-treated).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34967576", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We obtained 175 DEGs from the two samples (tamoxifen-resistant and paeoniflorin-treated)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We obtained 175 DEGs from the two samples (tamoxifen-resistant and paeoniflorin-treated).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34967576"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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