Proteome profiling of salivary small extracellular vesicles in glioblastoma patients

Juliana Müller Bark; Lucas Trevisan França de Lima; Xi Zhang; Daniel Broszczak; Paul J Leo; Rosalind L Jeffree; Benjamin Chua; Bryan W Day; Chamindie Punyadeera

doi:10.1002/cncr.34888

Proteome profiling of salivary small extracellular vesicles in glioblastoma patients

Cancer. 2023 Sep 15;129(18):2836-2847. doi: 10.1002/cncr.34888. Epub 2023 May 31.

Authors

Juliana Müller Bark^{1

2

3}, Lucas Trevisan França de Lima^{1

2

3

4}, Xi Zhang^{1

2

3}, Daniel Broszczak⁵, Paul J Leo^{3

6}, Rosalind L Jeffree^{7

8}, Benjamin Chua^{7

9}, Bryan W Day¹⁰, Chamindie Punyadeera^{1

2

11}

Affiliations

¹ Centre for Biomedical Technologies, The School of Biomedical Sciences, Faculty of Health, 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 Translational Research Institute, Brisbane, Queensland, Australia.
⁴ Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, Queensland, Australia.
⁵ School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia.
⁶ Translational Genomics Group, Queensland University of Technology, Translational Research Institute, Woolloongabba, Queensland, Australia.
⁷ Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.
⁸ Kenneth G. Jamieson Department of Neurosurgery, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.
⁹ Cancer Care Services, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
¹⁰ Cell and Molecular Biology Department, Sid Faithfull Brain Cancer Laboratory, QIMR Berghofer MRI, Brisbane, Queensland, Australia.
¹¹ Menzies Health Institute (MHIQ), Griffith University, Gold Coast, Queensland, Australia.

Abstract

Background: Extracellular vesicles (EVs) play a critical role in intercellular communication under physiological and pathological conditions, including cancer. EVs cargo reflects their cell of origin, suggesting their utility as biomarkers. EVs are detected in several biofluids, and their ability to cross the blood-brain barrier has highlighted their potential as prognostic and diagnostic biomarkers in gliomas, including glioblastoma (GBM). Studies have demonstrated the potential clinical utility of plasma-derived EVs in glioma. However, little is known about the clinical utility of saliva-derived EVs in GBM.

Methods: Small EVs were isolated from whole mouth saliva of GBM patients pre- and postoperatively. Isolation was performed using differential centrifugation and/or ultracentrifugation. EVs were characterized by concentration, size, morphology, and EVs cell-surface protein markers. Protein cargo in EVs was profiled using mass spectrometry.

Results: There were no statistically significant differences in size and concentration of EVs derived from pre- and post GBM patients' saliva samples. A higher number of proteins were detected in preoperative samples compared to postoperative samples. The authors found four highly abundant proteins (aldolase A, 14-3-3 protein ε, enoyl CoA hydratase 1, and transmembrane protease serine 11B) in preoperative saliva samples from GBM patients with poor outcomes. Functional enrichment analysis of pre- and postoperative saliva samples showed significant enrichment of several pathways, including those related to the immune system, cell cycle and programmed cell death.

Conclusions: This study, for the first time, demonstrates the feasibility of isolating and characterizing small EVs from pre- and postoperative saliva samples from GBM patients. Preliminary findings encourage further large cohort validation studies on salivary small EVs to evaluate prognosis in GBM.

Keywords: biomarkers; extracellular vesicles; glioblastoma; mass spectrometry; proteomics; saliva.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers / metabolism
Extracellular Vesicles* / metabolism
Extracellular Vesicles* / pathology
Glioblastoma* / pathology
Glioma* / pathology
Humans
Proteome / metabolism

Substances

Proteome
Biomarkers