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Comprehensive serum metabolic snapshots enable diagnosis, prognosis, and monitoring for brainstem gliomas [II]

ABSTRACT: Comprehensive serum metabolic snapshots enable diagnosis, prognosis, and monitoring for brainstem gliomas [II]

PROVIDER: PRJNA1242776 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32894200_1.fastq.gz	Fastqsanger.gz
	SRR32894200_2.fastq.gz	Fastqsanger.gz
	SRR32894201_1.fastq.gz	Fastqsanger.gz
	SRR32894201_2.fastq.gz	Fastqsanger.gz
	SRR32894202_1.fastq.gz	Fastqsanger.gz

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Comprehensive serum metabolic snapshots enable diagnosis, prognosis, and monitoring for brainstem gliomas [I]

Project description:Comprehensive serum metabolic snapshots enable diagnosis, prognosis, and monitoring for brainstem gliomas [I]

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Comprehensive serum metabolic snapshots enable diagnosis, prognosis, and monitoring for brainstem gliomas [II]

Project description:Brainstem gliomas (BSG) is a highly malignant central nervous system childhood tumors with a poor prognosis of a 5-year survival rate of < 10%. Metabolism during radiotherapy is a dynamic and precisely programmed process, improving clinical outcomes and guiding therapy decisions of BSG. Here, we for the first time construct diagnostic and prognostic assays of BSG via circulating metabolites based on both cross-sectional study and longitudinal cohort study with 106 BSG patients. We employ nanoparticle enhanced laser desorption/ionization mass spectrometry to characterize high-resolution static and dynamic snapshots of metabolites during BSG radiotherapy. We show that this serological tool reaches the area under the curve of 0.933 for BSG diagnosis in an independent blind test and predicts risk of patients with significant differences (p < 0.05) in prognostic outcomes. We further identify eight distinct temporal patterns of metabolite regulation associated with radiotherapy responses and tracked the metabolic trajectory via dynamic metabolic snapshots throughout radiotherapy process. If further validated, this framework could be extended to derive comprehensive metabolic pictures for cancers including but not limited to BSG.

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Project description:Purpose: More than 90% of children with diffuse intrinsic pontine glioma (DIPG) die within 2 years of diagnosis. There is a dire need to identify therapeutic targets, however lack of patient material for research has limited progress. We evaluated a large cohort of diffuse intrinsic pontine gliomas (DIPGs) to identify recurrent genomic abnormalities and gene expression signatures underlying DIPG. Patients and Methods: We used single nucleotide polymorphism arrays to evaluate genomic copy number imbalances in 43 DIPGs from 40 patients and in 8 low-grade exophytic brainstem gliomas. Gene expression arrays were used to evaluate expression signatures from 27 DIPGs, 6 low-grade exophytic brainstem gliomas and 66 low-grade gliomas arising outside the brainstem. Results: Frequencies of specific large-scale and focal imbalances varied significantly between DIPGs and pediatric glioblastomas outside the brainstem. Focal amplifications of genes within the receptor tyrosine kinase-Ras-PI3-kinase signaling pathway were found in 47% of DIPG, with PDGFRA and MET showing the highest frequency. 30% of DIPG contained focal amplifications of cell-cycle regulatory genes controlling RB phosphorylation, and 21% had concurrent amplification of genes from both pathways. Some tumors showed heterogeneity in amplification patterns. DIPGs showed distinct gene expression signatures relating to developmental processes compared to pediatric glioblastomas arising outside the brainstem, while expression signatures of low-grade exophytic brainstem gliomas were similar to low-grade gliomas outside the brainstem. Copy number analaysis: 43 DIPG samples, 8 Low Grade Gliomas using SNP6.0. Available matched normals are also profiled with SNP6.0. Expression analysis: 29 DIPG samples, 6 Low grade samples Please contact Suzanne Baker at Suzanne.Baker@stjude.org for CEL files and genotype calls.

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