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

Author:

Muller Bark Juliana123ORCID,Karpe Avinash V.45,Doecke James D.6,Leo Paul37,Jeffree Rosalind L.891011,Chua Benjamin912,Day Bryan W.3911,Beale David J.4,Punyadeera Chamindie21314ORCID

Affiliation:

1. Faculty of Health, Centre for Biomedical Technologies School of Biomedical Sciences, Queensland University of Technology Brisbane Queensland Australia

2. Saliva and Liquid Biopsy Translational Laboratory Griffith Institute for Drug Discovery – Griffith University Brisbane Queensland Australia

3. Faculty of Health School of Biomedical Sciences, Queensland University of Technology Gardens Point Queensland Australia

4. Environment, Commonwealth Scientific and Industrial Research Organization (CSIRO), Ecosciences Precinct Dutton Park Queensland Australia

5. Agriculture and Food Commonwealth Scientific and Industrial Research Organization (CSIRO) Acton Australian Capital Territory Australia

6. Australian eHealth Research Centre, CSIRO. Level 7, Surgical Treatment and Rehabilitation Service – STARS Royal Brisbane and Women's Hospital Herston Queensland Australia

7. Faculty of Health, Translational Genomics Group School of Biomedical Sciences, Queensland University of Technology Woolloongabba Australia

8. QIMR Berghofer Medical Research Institute Herston Queensland Australia

9. Faculty of Medicine University of Queensland Herston Queensland Australia

10. Kenneth G. Jamieson Department of Neurosurgery Royal Brisbane and Women's Hospital Brisbane Queensland Australia

11. Cell and Molecular Biology Department, Sid Faithfull Brain Cancer Laboratory QIMR Berghofer MRI Brisbane Queensland Australia

12. Cancer Care Services Royal Brisbane and Women's Hospital Brisbane Queensland Australia

13. Menzies Health Institute, Griffith University Southport Queensland Australia

14. Translational Research Institute Woolloongabba Queensland Australia

Abstract

AbstractBackgroundDespite 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.MethodsSaliva 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.ResultsAltogether, 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.ConclusionOur 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.

Funder

Royal Brisbane and Women's Hospital Foundation

Cancer Australia

Cure Brain Cancer Foundation

Publisher

Wiley

Subject

Cancer Research,Radiology, Nuclear Medicine and imaging,Oncology

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