Salivary micro RNAs as biomarkers for oropharyngeal cancer

Author:

Ekanayake Weeramange Chameera1234,Tang Kai Dun35,Barrero Roberto A.6,Hartel Gunter7,Liu Zhen89,Ladwa Rahul910,Langton‐Lockton Julian11,Frazer Ian9,Kenny Lizbeth912,Vasani Sarju189,Punyadeera Chamindie12ORCID

Affiliation:

1. Saliva and Liquid Biopsy Translational Laboratory Griffith Institute for Drug Discovery (GRIDD) and Menzies Health Institute Queensland (MIHQ) Griffith University Nathan Queensland Australia

2. Menzies Health Institute Queensland (MIHQ) Griffith University Nathan Queensland Australia

3. School of Biomedical Science Centre for Biomedical Technologies Faculty of Health Queensland University of Technology Brisbane Queensland Australia

4. Department of Medical Laboratory Sciences Faculty of Health Sciences The Open University of Sri Lanka Nugegoda Sri Lanka

5. EDA School of Biological Sciences and Biotechnology and Nankai International Advanced Research Institute (Shenzhen Futian) Nankai University Tianjin People's Republic of China

6. eResearch, Academic Division Queensland University of Technology Brisbane Queensland Australia

7. Statistics Unit QIMR Berghofer Medical Research Institute Herston Queensland Australia

8. Department of Otolaryngology Royal Brisbane and Women's Hospital Brisbane Queensland Australia

9. Faculty of Medicine The University of Queensland Herston Queensland Australia

10. Department of Cancer Care Services Princess Alexandra Hospital Woolloongabba Queensland Australia

11. Metro‐North Sexual Health and HIV Service Brisbane Queensland Australia

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

Abstract

AbstractBackgroundDespite the rising incidence, particularly of the human papillomavirus (HPV)‐associated fraction of oropharyngeal cancer (OPC), there are no early detection methods for OPC. Considering the close association between saliva and head and neck cancers, this study was designed to investigate salivary micro RNA (miRNAs) associated with OPC, especially focusing on HPV‐positive OPC.MethodsSaliva was collected from OPC patients at diagnosis and patients were clinically followed up ≤5 years. Salivary small RNA isolated from HPV‐positive OPC patients (N = 6), and HPV‐positive (N = 4) and negative controls (N = 6) were analysed by next‐generation sequencing to identify dysregulated miRNAs. Discovered miRNAs were validated by quantitative PCR using two different assays in a separate cohort of patients (OPC = 91, controls = 92). The relative expression was calculated considering SNORD‐96A as the normalizer. Candidate miRNAs with diagnostic and prognostic potential were evaluated by generalized logistic regression.ResultsA panel consisting of nine miRNAs was identified to have the best diagnostic performance to discriminate HPV‐positive OPC from HPV‐positive controls (AUC‐ validation‐1 = 94.8%, validation‐2 = 98%). Further, a panel consisting of six miRNAs were identified to discriminate OPC from controls regardless of the HPV status (AUC‐ validation‐1 = 77.2%, validation‐2 = 86.7%). In addition, the downregulation of hsa‐miR‐7‐5p was significantly associated with poor overall survival of OPC patients (HR = 0.638). A panel consisting of nine miRNAs were identified for the prediction of the overall survival of the OPC patients (log‐rank test‐p = 0.0008).ConclusionThis study highlights that salivary miRNAs can play an essential role in the detection and prognostication of OPC.

Funder

Cancer Australia

Department of Health, Australian Government

Publisher

Wiley

Subject

Cancer Research,Radiology, Nuclear Medicine and imaging,Oncology

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