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pmid:31528121
Prognostic significance of TOP2A in non-small cell lung cancer revealed by bioinformatic analysis.
Wenxia Ma · Bin Wang · Yaping Zhang · Ziyue Wang · Dan Niu · Siyu Chen · Zhirong Zhang · Ningning Shen · Weixia Han · Xiaoqin Zhang · Rong Wei · Chen Wang
Cancer cell international · 2019 doi:10.1186/s12935-019-0956-1
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Experiment
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Complete file
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The study is designed to identify new prognostic predictors and potential gene targets based on bioinformatic analysis of Gene Expression Omnibus (GEO) database.\nMETHODS: Four cDNA expression profiles GSE19188, GSE101929, GSE18842 and GSE33532 were chosen from GEO database to analyze the differently expressed genes (DEGs) between non-small cell lung cancer (NSCLC) and normal lung tissues. After the DEGs functions were analyzed, the protein-protein interaction network (PPI) of DEGs were constructed, and the core gene in the network which has high connectivity degree with other genes was identified. We analyzed the association of the gene with the development of NSCLC as well as its prognosis. Lastly we explored the conceivable signaling mechanism of the gene regulation during the development of NSCLC.\nRESULTS: A total of 92 up regulated and 214 down regulated DEGs were shared in four cDNA expression profiles. Based on their PPI network, TOP2A was connected with most of other genes and was selected for further analysis. Kaplan-Meier overall survival analysis (OS) revealed that TOP2A was associated with worse NSCLC patients survival. And both GEPIA analysis and immunohistochemistry experiment (IHC) confirmed that TOP2A was aberrant gain of expression in cancer comparing to normal tissues. The clinical significance of TOP2A and probable signaling pathways it involved in were further explored, and a positive correlation between TOP2A and TPX2 expression was found in lung cancer tissues.\nCONCLUSION: Using bioinformatic analysis, we revealed that TOP2A could be adopted as a prognostic indicator of NSCLC and it potentially regulate cancer development through co-work with TPX2. However, more detailed experiments are needed to clarify its drug target role in clinical medical use.", "claims": [{"id": "claim-method", "statement": "In the study, we used Kaplan–Meier plotter to analyze the correlation between TOP2A gene and NSCLC patients OS, followed by drawing the survival curve.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31528121", "locator": "sections[6] \"Kaplan–Meier survival analysis\" paragraph 2", "quote": "In the study, we used Kaplan–Meier plotter to analyze the correlation between TOP2A gene and NSCLC patients OS, followed by drawing the survival curve."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analyzed during this study are included in this published article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31528121", "locator": "sections[29] \"notes\" paragraph 1", "quote": "All data generated or analyzed during this study are included in this published article."}], "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:31528121"], "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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"column_count": 7, "numeric_cells": 27, "header_rows": 2, "locator": "section[19]/table-wrap[1]#Tab3"}}, {"id": "asset:table:pmid:31528121:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d4cb7cbcf01f876c42ba0b4c5fadeefaf07d2b209a06a5ac9a02b4fb85b3cd8d", "bytes": 800, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[20]/table-wrap[1]#Tab4", "version": null, "note": "Biological process events centered on TOP2A", "structure": {"pmcid": "PMC6737627", "section_index": 20, "section_title": "TOP2A centered signaling pathways", "row_count": 6, "column_count": 5}, "table": {"label": "Table 4", "caption": "Biological process events centered on TOP2A", "rows": [["Description", "Counts", "Background gene counts", "FDR", "Matching proteins in the network"], ["Mitotic cell cycle", "10", "628", "9.19E−12", "BUB1, CCNB2, CDC20, CDK1, DLGAP5, NCAPG, PBK, TOP2A, TPX2, UBE2C"], ["Cell division", "9", "483", "6.67E−11", "BUB1, CCNB2, CDC20, CDK1, NCAPG, TOP1, TOP2A, TPX2, UBE2C"], ["Mitotic cell cycle process", "9", "564", "1.76E−10", "BUB1, CCNB2, CDC20, CDK1, DLGAP5, NCAPG, TOP2A, TPX2, UBE2C"], ["Nuclear division", "7", "268", "4.29E−09", "BUB1, CDC20, DLGAP5, NCAPG, TOP2A, TPX2, UBE2C"], ["Chromosome segregation", "6", "253", "1.89E−07", "BUB1, CDC20, DLGAP5, NCAPG, TOP1, TOP2A"]], "row_count": 6, "column_count": 5, "numeric_cells": 20, "header_rows": 1, "locator": "section[20]/table-wrap[1]#Tab4"}}, {"id": "asset:table:pmid:31528121:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b942dbdb59423a3020954188622fbbbb00c8fb1ef3793963fd43ff70fc17c9fa", "bytes": 804, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[20]/table-wrap[2]#Tab5", "version": null, "note": "KEGG signaling pathways centered on 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