Integrated Proteomic and Metabolomic Analyses of Cerebrospinal Fluid from Pediatric Patients with Diffuse Intrinsic Pontine Glioma.
This human observational study reports integrated CSF proteomic and metabolomic profiling in pediatric DIPG, identifying numerous differential proteins, 40 differential metabolites, and convergent enrichment of purine metabolism alongside complement/coagulation and tyrosine-metabolism signals.
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This human observational study reports integrated CSF proteomic and metabolomic profiling in pediatric DIPG, identifying numerous differential proteins, 40 differential metabolites, and convergent enrichment of purine metabolism alongside complement/coagulation and tyrosine-metabolism signals.
Research significance
The reported multiomic convergence provides evidence that purine metabolism is altered in DIPG-associated CSF; it can be hypothesized—but is not demonstrated here—that purine-pathway components could serve as biomarkers or therapeutic targets after tumor-specificity, causal relevance, and druggability are validated.
Source abstract
Diffuse intrinsic pontine glioma (DIPG) is a rare and fatal pediatric brainstem malignancy for which effective treatment options are lacking. Cerebrospinal fluid (CSF) analysis can reveal intrinsic alterations and characteristic metabolic profiles of the tumor microenvironment. In this study, the proteome and metabolome of CSF from DIPG patients were comprehensively analyzed to identify potential biomarkers and the pathways involved. Functional annotation and pathway enrichment analyses were performed using the GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) databases. Bioinformatics methods were used to comprehensively analyze the proteomic and metabolomic results to identify key differentially expressed proteins, metabolites, and potential signaling pathways involved in DIPG. In total, 885 DEPs (differentially expressed proteins) were identified in cerebrospinal fluid from DIPG patients, of which 54 were upregulated and 831 were downregulated, primarily originating from the cytoplasm and cell membrane. Among the top 20 upregulated proteins, URB1 (nucleolar pre-ribosomal-associated protein 1) had the greatest statistical significance, while the remaining proteins were mostly immunoglobulin fragments. GO enrichment analysis revealed that the downregulated proteins were enriched primarily in cellular processes, metabolic processes, and binding functions. KEGG analysis revealed that upregulated proteins were significantly enriched in complement and coagulation cascades, whereas downregulated proteins were primarily associated with endocytosis and certain microbial infections. A total of 1372 metabolites were identified, of which 40 were differentially expressed: 24 were upregulated, and 16 were downregulated. Pathway analyses of the differentially expressed metabolites revealed that they were primarily related to purine metabolism and tyrosine metabolism. The multiomics analysis revealed that purine metabolism is particularly important in DIPG.