Dataset Information

A pilot study: Metabolic profiling of plasma and saliva samples from newly diagnosed glioblastoma patients.

ABSTRACT:

Background

Despite aggressive treatment, more than 90% of glioblastoma (GBM) patients experience recurrences. GBM response to therapy is currently assessed by imaging techniques and tissue biopsy. However, difficulties with these methods may cause misinterpretation of treatment outcomes. Currently, no validated therapy response biomarkers are available for monitoring GBM progression. Metabolomics holds potential as a complementary tool to improve the interpretation of therapy responses to help in clinical interventions for GBM patients.

Methods

Saliva and blood from GBM patients were collected pre and postoperatively. Patients were stratified conforming their progression-free survival (PFS) into favourable or unfavourable clinical outcomes (>9 months or PFS ≤ 9 months, respectively). Analysis of saliva (whole-mouth and oral rinse) and plasma samples was conducted utilising LC-QqQ-MS and LC-QTOF-MS to determine the metabolomic and lipidomic profiles. The data were investigated using univariate and multivariate statistical analyses and graphical LASSO-based graphic network analyses.

Results

Altogether, 151 metabolites and 197 lipids were detected within all saliva and plasma samples. Among the patients with unfavourable outcomes, metabolites such as cyclic-AMP, 3-hydroxy-kynurenine, dihydroorotate, UDP and cis-aconitate were elevated, compared to patients with favourable outcomes during pre-and post-surgery. These metabolites showed to impact the pentose phosphate and Warburg effect pathways. The lipid profile of patients who experienced unfavourable outcomes revealed a higher heterogeneity in the abundance of lipids and fewer associations between markers in contrast to the favourable outcome group.

Conclusion

Our findings indicate that changes in salivary and plasma metabolites in GBM patients can potentially be employed as less invasive prognostic biomarkers/biomarker panel but validation with larger cohorts is required.

SUBMITTER: Muller Bark J

PROVIDER: S-EPMC10242862 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A pilot study: Metabolic profiling of plasma and saliva samples from newly diagnosed glioblastoma patients.

Muller Bark Juliana J Karpe Avinash V AV Doecke James D JD Leo Paul P Jeffree Rosalind L RL Chua Benjamin B Day Bryan W BW Beale David J DJ Punyadeera Chamindie C

Cancer medicine 20230409 10

<h4>Background</h4>Despite aggressive treatment, more than 90% of glioblastoma (GBM) patients experience recurrences. GBM response to therapy is currently assessed by imaging techniques and tissue biopsy. However, difficulties with these methods may cause misinterpretation of treatment outcomes. Currently, no validated therapy response biomarkers are available for monitoring GBM progression. Metabolomics holds potential as a complementary tool to improve the interpretation of therapy responses t ...[more]

PMID: 37031458

Similar Datasets

Project description:Background:O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status is a predictive biomarker in glioblastoma patients. Glioblastoma without hypermethylated MGMT promoter is largely resistant to treatment with temozolomide. These patients are in particular need of new treatment approaches, which are offered by biomarker-driven clinical trials with targeted drugs based on molecular characterization of individual tumors. Methods:In preparation for an upcoming clinical study, a comprehensive molecular profiling approach was undertaken on tissues from 43 glioblastoma patients harboring an unmethylated MGMT promoter at diagnosis. The diagnostic pipeline covered various levels of molecular characteristics, including whole-exome sequencing, low-coverage whole-genome sequencing, RNA sequencing, as well as microarray-based gene expression profiling and DNA methylation arrays. Results:Complex multilayer molecular diagnostics were feasible in this setting with a median turnaround time of 4-5 weeks from surgery to the molecular tumor board. In 35% of cases, potentially relevant therapeutic decisions were derived from the data. Alterations were most frequently found in receptor tyrosine kinases, members of the phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin and mitogen-activated protein kinase pathway as well as cell cycle control and p53 regulation cascades. Individual tumors harbored clonal alterations such as oncogenic fusions of tyrosine kinases which constitute promising targets for targeted therapies. A prioritization algorithm is proposed to allocate patients with multiple targets to the potentially best treatment option. Conclusion:With this feasibility study, a comprehensive molecular profiling approach for patients with newly diagnosed glioblastoma harboring an unmethylated MGMT promoter is presented. Analyses in this pilot cohort serve as a basis for trials based on targetable alterations and on the question of allocation of patients to the best treatment arm.

Dataset Information

A pilot study: Metabolic profiling of plasma and saliva samples from newly diagnosed glioblastoma patients.

Background

Methods

Results

Conclusion

Publications

A pilot study: Metabolic profiling of plasma and saliva samples from newly diagnosed glioblastoma patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets