Abstract
Neuroblastoma is a childhood malignancy with high morbidity and mortality. We identified key biomarkers associated with neuroblastoma risk and prognosis. The gene modules most associated with neuroblastoma risk were derived by WGCNA. Modular genes were intersected with differentially expressed genes between patients with high-risk (HR) and non-high-risk (NHR) to obtain risk genes, and enrichment analysis was performed. After incorporating risk genes into Cox regression analysis, LASSO algorithm, and K-M survival analysis, key genes were identified and introduced into four external datasets for validation. We performed short time-series expression miner analysis and single-sample genome enrichment analysis. Finally, we evaluated the difference in DNA methylation levels to identify meaningful methylation marks. We identified 5 key genes (ANO6, CPNE2, DST, PLXNC1, SCN3A) for neuroblastoma risk and prognosis, which correlated closely with known neuroblastoma biomarkers. All key genes showed a progressive downregulation trend with increasing risk levels of neuroblastoma. The immune infiltration of 14 immune cells was significantly different between HR-NB and NHR-NB, and most immune cells were negatively correlated with key genes. Furthermore, the expression of ANO6, CPNE2, DST, and PLXNC1 was modified by DNA methylation. This study identified 5 key genes for neuroblastoma risk and prognosis that were potential biomarkers.
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Data Availability
The datasets analyzed during the current study are available in the Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/) database, the R2: Genomics Analysis and Visualization Platform (https://hgserver1.amc.nl/cgi-bin/r2/main.cgi), and Therapeutically Applicable Research to Generate Effective Treatments (https://ocg.cancer.gov/programs/target) database.
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All authors contributed to the study conception and design. Jiao Zhang provided ideas and carried out research and design. Material preparation, data collection, and data analysis were completed by Jiao Zhang, Yahui Han, Dun Yan, and Da Zhang. The first draft of the manuscript was completed by Yahui Han and Diming Zhou, modified by Xiafei Yuan and Wei Zhao, and determined by Jiao Zhang. All authors read and approved the final manuscript.
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Zhang, J., Han, Y., Yan, D. et al. Identification of Key Genes Associated with Risk and Prognosis of Neuroblastoma. J Mol Neurosci 72, 2398–2412 (2022). https://doi.org/10.1007/s12031-022-02087-7
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DOI: https://doi.org/10.1007/s12031-022-02087-7