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Analysis and identification of novel biomarkers involved in neuroblastoma via integrated bioinformatics

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Summary

Neuroblastoma (NB) is the most common extracranial solid tumor in children. Under various treatments, some patients still have a poor prognosis. Hence, it is necessary to find new valid targets for NB therapy. In this study, a comprehensive bioinformatic analysis was used to identify differentially expressed genes (DEGs) between NB and control cells, and to select hub genes associated with NB. GSE66586 and GSE78061 datasets were downloaded from the Gene Expression Omnibus (GEO) database and DEGs were selected. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied to the selected DEGs. The STRING database and Cytoscape software were used to construct protein-protein interaction (PPI) networks and perform modular analysis of the DEGs. The R2 database was used for prognostic analysis. We identified a total of 238 DEGs from two microarray databases. GO enrichment analysis shows that these DEGs are mainly concentrated in the regulation of cell growth, cell migration, cell fate determination, and cell maturation. KEGG pathway analysis showed that these DEGs are mainly involved in focal adhesion, the TNF signaling pathway, cancer-related pathways, and signaling pathways regulating stem cell pluripotency. We identified the 15 most closely related DEGs from the PPI network, and performed R2 database prognostic analysis to select five hub genes – CTGF, EDN1, GATA2, LOX, and SERPINE1. This study distinguished hub genes and related signaling pathways that can potentially serve as diagnostic indicators and therapeutic biomarkers for NB, thereby improving understanding of the molecular mechanisms involved in NB.

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Acknowledgements

We thank the staff from Medical Research Center of Shengjing Hospital who gave us support throughout the experiments.

Funding

The work was supported by the National Natural Science Foundation of China (No. 81972515, 81,472,359), Key Research and Development Foundation of Liaoning Province (2019JH8/10300024), 2013 Liaoning Climbing Scholar Foundation, and 345 Talent Project of Shengjing Hospital of China Medical University.

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  1. Bo Chen and Peng Ding contributed equally to this work.

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  1. Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China

    Bo Chen, Peng Ding, Zhongyan Hua, Xiuni Qin & Zhijie Li

  2. Medical Research Center, Liaoning Key Laboratory of Research and Application of Animal Models for Environmental and Metabolic Diseases, Shengjing Hospital of China Medical University, #36 Sanhao Street, Heping District, Shenyang, 110004, China

    Bo Chen, Peng Ding, Zhongyan Hua, Xiuni Qin & Zhijie Li

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Bo Chen and Peng Ding had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Both contributed equally to the study and are co-first authors; Zhongyan Hua and Xiuni Qin contributed to collection of data; Zhijie Li contributed to the study design, interpretation of the data, the writing of the manuscript, and the submission of the manuscript for publication.

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Chen, B., Ding, P., Hua, Z. et al. Analysis and identification of novel biomarkers involved in neuroblastoma via integrated bioinformatics. Invest New Drugs 39, 52–65 (2021). https://doi.org/10.1007/s10637-020-00980-9

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