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Proteomic Alterations in Salivary Exosomes Derived from Human Papillomavirus-Driven Oropharyngeal Cancer

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Abstract

Background

Increasing evidence supports the notion that human papillomavirus (HPV) DNA integration onto the human genome can influence and alter the molecular cargo in the exosomes derived from head and neck cancer cells. However, the molecular cargo of salivary exosomes derived from HPV-driven oropharyngeal cancer (HPV-driven OPC) remains unelucidated.

Methods and materials

Salivary exosomes morphology and molecular characterizations were examined using the nanoparticle tracking (NTA), western blot analysis, transmission electron microscopy (TEM) and mass spectrometry analysis.

Results

We report that HPV16 DNA was detected (80%) in isolated salivary exosomes of HPV-driven OPC patients. Importantly, we demonstrate elevated protein levels of six main glycolytic enzymes [i.e., aldolase (ALDOA), glyceraldehye-3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase A/B (LDHA and LDHB), phosphoglycerate kinase 1 (PGK1) and pyruvate kinase M1/2 (PKM)] in isolated salivary exosomes of HPV-driven OPC patients, suggesting a novel mechanism underlying the potential role of salivary exosomes in mediating the reciprocal interplay between glucose metabolism and HPV-driven OPC.

Conclusion

Our data demonstrate the potential diagnostic value of HPV16 DNA and glycolytic enzymes in salivary exosomes in discriminating healthy controls from HPV-driven OPC patients, thereby opening new avenues in the future for clinical translation studies.

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Acknowledgements

We would like to thank the members of Saliva and Liquid Biopsy Translational Laboratory for their assistance in sample collection and processing. We also thank Dana Middleton and the staff at the Princess Alexandra Hospital for their assistance in the recruitment of study patients and collection of clinical samples. In addition, we thank the volunteers who took part in this study.

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Authors and Affiliations

  1. Saliva and Liquid Biopsy Translational Laboratory, The Translational Research Institute, The School of Biomedical Sciences, Queensland University of Technology (QUT), 60 Musk Avenue, GPO Box 2434, Brisbane, QLD, 4059, Australia

    Kai Dun Tang, Yunxia Wan, Xi Zhang, Natalie Bozyk & Chamindie Punyadeera

  2. Department of Otolaryngology, Royal Brisbane and Women’s Hospital, Herston, QLD, 4029, Australia

    Sarju Vasani

  3. Royal Brisbane and Women’s Hospital, Central Integrated Regional Cancer Service, The University of Queensland School of Medicine, Queensland Health, Brisbane, QLD, 4029, Australia

    Liz Kenny

Authors
  1. Kai Dun Tang
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  2. Yunxia Wan
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  3. Xi Zhang
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  4. Natalie Bozyk
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  5. Sarju Vasani
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  6. Liz Kenny
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  7. Chamindie Punyadeera
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Corresponding author

Correspondence to Chamindie Punyadeera.

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Funding

CP is currently receiving funding from Cancer Australia (APP1145657), NHMRC Ideas Grant (APP 2002576), National Institutes of Health (NIH) (1R21EB030349-01), Garnett Passes and Rodney Williams Foundation and Royal Brisbane Women’s Hospital Foundation.

Conflict of interest

The authors declare that there is no conflict of interest

Ethics approval

This study was approved by the Medical Ethical Institutional Board of University of Queensland (HREC No: 2014000862); Queensland University of Technology (HREC No: 1400000617 and 1400000641) and by the Princess Alexandra Hospital (PAH) Ethics Review Board (HREC Number: HREC/12/QPAH/381), following the Declaration of Helsinki 1964 and its later amendments or comparable ethical standards.

Consent to participate

All participants provided written informed consent, prior to saliva sample collection.

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All datasets generated for this study are included in the article.

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Author contributions

All authors have read and agree to the published version of the manuscript. KDT, YX and CP: conceptualization. All authors: methodology, validation, formal analysis, data curation, investigation, and writing—review and editing. KDT: writing—original draft preparation. CP: funding acquisition.

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Tang, K.D., Wan, Y., Zhang, X. et al. Proteomic Alterations in Salivary Exosomes Derived from Human Papillomavirus-Driven Oropharyngeal Cancer. Mol Diagn Ther 25, 505–515 (2021). https://doi.org/10.1007/s40291-021-00538-2

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  • DOI: https://doi.org/10.1007/s40291-021-00538-2

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