Abstract
Background
Aberrant DNA methylation is one of the major epigenetic alterations in neuroblastoma.
Objective
Exploring the prognostic significance of methylation driver genes in neuroblastoma could help to comprehensively assess patient prognosis.
Methods
After identifying methylation driver genes (MDGs), we used the LASSO algorithm and stepwise Cox regression to construct methylation driver gene-related risk score (MDGRS), and evaluated its predictive performance by multiple methods. By combining risk grouping and MDGRS grouping, we developed a new prognostic stratification strategy and explored the intrinsic differences between the different groupings.
Results
We identified 44 stably expressed MDGs in neuroblastoma. MDGRS showed superior predictive performance in both internal and external cohorts and was strongly correlated with immune-related scores. MDGRS can be an independent prognostic factor for neuroblastoma, and we constructed the nomogram to facilitate clinical application. Based on the new prognostic stratification strategy, we divided the patients into three groups and found significant differences in overall prognosis, clinical characteristics, and immune infiltration between the different subgroups.
Conclusion
MDGRS was an accurate and promising tool to facilitate comprehensive pre-treatment assessment. And the new prognostic stratification strategy could be helpful for clinical decision making.
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Data Availability
Publicly available datasets were used in this study. GSE73515 (PRJNA297203), GSE73517 (PRJNA297205), GSE49710 (PRJNA214798) and GSE62564 (PRJNA264621) are available in the Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/). E-MTAB-8248 is downloaded from the ArrayExpress database (https://www.ebi.ac.uk/arrayexpress/).
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Funding
This study was supported by grants from the National Natural Science Foundation of China (No: 81502187); Key scientific research projects of colleges and universities in Henan Province (No. 20A320020, Jiao Zhang); the Basic and Frontier Technology Research Project of Henan Province (No. 212102310032, Jiao Zhang).
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All authors contributed to the study conception and design. Jiao Zhang provided ideas and carried out research and design. Yahui Han and Biyun Li completed the material preparation, data collection and data analysis and contributed equally to this paper. The first draft of the manuscript was completed by Jian Cheng and Diming Zhou, modified by Xiafei Yuan, Wei Zhao and Da Zhang, and determined by Jiao Zhang. All authors read and approved the final manuscript.
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Han, Y., Li, B., Cheng, J. et al. Construction of methylation driver gene-related prognostic signature and development of a new prognostic stratification strategy in neuroblastoma. Genes Genom 46, 171–185 (2024). https://doi.org/10.1007/s13258-023-01483-6
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DOI: https://doi.org/10.1007/s13258-023-01483-6