Kai Dun Tang1, Yunxia Wan1, Xi Zhang1, Natalie Bozyk1, Sarju Vasani2, Liz Kenny3, Chamindie Punyadeera4. 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. 2. Department of Otolaryngology, Royal Brisbane and Women's Hospital, Herston, QLD, 4029, Australia. 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. 4. 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. chamindie.punyadeera@qut.edu.au.
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.
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.
Authors: Maura L Gillison; Tatevik Broutian; Robert K L Pickard; Zhen-you Tong; Weihong Xiao; Lisa Kahle; Barry I Graubard; Anil K Chaturvedi Journal: JAMA Date: 2012-01-26 Impact factor: 56.272
Authors: Angela Hong; C Soon Lee; Deanna Jones; Anne-Sophie Veillard; Mei Zhang; Xiaoying Zhang; Robert Smee; June Corry; Sandro Porceddu; Christopher Milross; Michael Elliott; Jonathan Clark; Barbara Rose Journal: Head Neck Date: 2015-06-25 Impact factor: 3.147
Authors: Gypsyamber D'Souza; Aimee R Kreimer; Raphael Viscidi; Michael Pawlita; Carole Fakhry; Wayne M Koch; William H Westra; Maura L Gillison Journal: N Engl J Med Date: 2007-05-10 Impact factor: 91.245
Authors: Jacques Ferlay; Isabelle Soerjomataram; Rajesh Dikshit; Sultan Eser; Colin Mathers; Marise Rebelo; Donald Maxwell Parkin; David Forman; Freddie Bray Journal: Int J Cancer Date: 2014-10-09 Impact factor: 7.396
Authors: Taylor D Ellington; S Jane Henley; Virginia Senkomago; Mary Elizabeth O'Neil; Reda J Wilson; Simple Singh; Cheryll C Thomas; Manxia Wu; Lisa C Richardson Journal: MMWR Morb Mortal Wkly Rep Date: 2020-04-17 Impact factor: 17.586