Abstract
Purpose
Cell death plays an important role in tumourigenesis and progression; nevertheless, the clinical significance of cell death-related genes in neuroblastoma remains incompletely understood.
Methods
We separately constructed the corresponding risk scores for each of the eight cell death pathways separately and assessed their predictive performance. Through Cox regression analysis, these eight risk scores were integrated to obtain final cell death risk scores (CDRS). We evaluated the predictive performance of CDRS in multiple datasets and compared its accuracy with the clinical characteristics of patients and some existing prognostic models for neuroblastoma. We then explored the differences in immune infiltration between the high and low CDRS groups, and the significance of CDRS on EFS and disease progression.
Results
All eight risk scores have high predictive accuracy, with the Immunogenic-RS being the most accurate and the cuproptosis-RS the least accurate. Model genes are mainly enriched in a variety of cancer-related pathways and are closely related to the clinical characteristics. CDRS showed superior and robust predictive performance in multiple datasets and was more accurate than the clinical characteristics of patients and some existing prognostic models for neuroblastoma. High CDRS group featured distinct immune cold tumor profiles and may have poorer immune checkpoint inhibitor efficacy. CDRS had significance in predicting EFS and disease progression.
Conclusion
We integrated risk scores associated with multiple cell death pathways to develop a high-performing and robust neuroblastoma signature. CDRS was a promising tool that may help with risk assessment and prediction of overall prognosis, and thus improve clinical outcomes.
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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 and the ArrayExpress database (https://www.ebi.ac.uk/arrayexpress/) database.
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All authors contributed to the study conception and design. JZ provided ideas and carried out research and design. Material preparation, data collection, and data analysis were completed by YH, BL, DY, and DZ. The first draft of the manuscript was completed by YH and BL, modified by XY, WZ, and DZ, and determined by JZ. All authors read and approved the final manuscript.
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Han, Y., Li, B., Yan, D. et al. Combining multiple cell death pathway-related risk scores to develop neuroblastoma cell death signature. J Cancer Res Clin Oncol 149, 6513–6526 (2023). https://doi.org/10.1007/s00432-023-04605-5
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DOI: https://doi.org/10.1007/s00432-023-04605-5