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pmid:33777535
Bioinformatics analysis identified CDC20 as a potential drug target for cholangiocarcinoma.
Prin Sungwan · Worachart Lert-Itthiporn · Atit Silsirivanit · Nathakan Klinhom-On · Seiji Okada · Sopit Wongkham · Wunchana Seubwai
PeerJ · 2021 doi:10.7717/peerj.11067
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Moreover, most CCA patients have a very poor outcome. Presently, there are still no effective treatment regimens for CCA. The resistance to several standard chemotherapy drugs occurs frequently; thus, searching for a novel effective treatment for CCA is urgently needed.\nMETHODS: In this study, comprehensive bioinformatics analyses for identification of novel target genes for CCA therapy based on three microarray gene expression profiles (GSE26566, GSE32225 and GSE76297) from the Gene Expression Omnibus (GEO) database were performed. Based on differentially expressed genes (DEGs), gene ontology and pathway enrichment analyses were performed. Protein-protein interactions (PPI) and hub gene identifications were analyzed using STRING and Cytoscape software. Then, the expression of candidate genes from bioinformatics analysis was measured in CCA cell lines using real time PCR. Finally, the anti-tumor activity of specific inhibitor against candidate genes were investigated in CCA cell lines cultured under 2-dimensional and 3-dimensional cell culture models.\nRESULTS: The three microarray datasets exhibited an intersection consisting of 226 DEGs (124 up-regulated and 102 down-regulated genes) in CCA. DEGs were significantly enriched in cell cycle, hemostasis and metabolism pathways according to Reactome pathway analysis. In addition, 20 potential hub genes in CCA were identified using the protein-protein interaction (PPI) network and sub-PPI network analysis. Subsequently, CDC20 was identified as a potential novel targeted drug for CCA based on a drug prioritizing program. In addition, the anti-tumor activity of a potential CDC20 inhibitor, namely dinaciclib, was investigated in CCA cell lines. Dinaciclib demonstrated huge anti-tumor activity better than gemcitabine, the standard chemotherapeutic drug for CCA.\nCONCLUSION: Using integrated bioinformatics analysis, CDC20 was identified as a novel candidate therapeutic target for CCA.", "claims": [{"id": "claim-method", "statement": "Statistical significance was determined by Students’ t test and P < 0.05 was noted as statistical significance.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33777535", "locator": "sections[11] \"Statistical analysis\" paragraph 2", "quote": "Statistical significance was determined by Students’ t test and P < 0.05 was noted as statistical significance."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Raw measurements are available in the Supplemental Files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33777535", "locator": "sections[21] \"Additional Information and Declarations\" paragraph 4", "quote": "Raw measurements are available in the Supplemental Files."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:33777535"], "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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