Metabolomics-transcriptomics joint analysis: unveiling the dysregulated cell death network and developing a diagnostic model for high-grade neuroblastoma.

High-grade neuroblastoma (HG-NB) exhibits a significantly diminished survival rate in comparison to low-grade neuroblastoma (LG-NB), primarily attributed to the mechanism of HG-NB is unclear and the lacking effective therapeutic targets and diagnostic model. Therefore, the current investigation aims to study the dysregulated network between HG-NB and LG-NB based on transcriptomics and metabolomics joint analysis. Meanwhile, a risk diagnostic model to distinguish HG-NB and LG-NB was also developed. Metabolomics analysis was conducted using plasma samples obtained from 48 HG-NB patients and 36 LG-NB patients. A total of 39 metabolites exhibited alterations, with 20 showing an increase and 19 displaying a decrease in HG-NB. Additionally, transcriptomics analysis was performed on NB tissue samples collected from 31 HG-NB patients and 20 LG-NB patients. Results showed that a significant alteration was observed in a total of 1,199 mRNAs in HG-NB, among which 893 were upregulated while the remaining 306 were downregulated. In particular, the joint analysis of both omics data revealed three aberrant pathways, namely the cAMP signaling pathway, PI3K-Akt signaling pathway, and TNF signaling pathway, which were found to be associated with cell death. Notably, a diagnostic model for HG-NB risk classification was developed based on the genes , , and with an area under the receiver operating characteristic curve of 0.915. In the validation set, the sensitivity and specificity were determined to be 75.0% and 80.0%, respectively.