Plasma miR-151-3p as a Candidate Diagnostic Biomarker for Head and Neck Cancer: A Cross-sectional Study within the INHANCE Consortium

Author:

Pastorino Roberta12ORCID,Sassano Michele23ORCID,Danilo Tiziano Francesco45ORCID,Giraldi Luca2ORCID,Amore Rosarita2ORCID,Arzani Dario2ORCID,Abiusi Emanuela45ORCID,Ahrens Wolfgang6ORCID,Vilches Laia Alemany78ORCID,Canova Cristina9ORCID,Healy Claire Mary10ORCID,Holcatova Ivana11ORCID,Lagiou Pagona12ORCID,Polesel Jerry13ORCID,Popovic Maja14ORCID,Nygård Ståle15ORCID,Cadoni Gabriella1617ORCID,Znaor Ariana18ORCID,Boffetta Paolo319ORCID,Matsuo Keitaro2021ORCID,Oze Isao20ORCID,Brennan Paul18ORCID,Boccia Stefania12ORCID

Affiliation:

1. 1Department of Woman and Child Health and Public Health—Public Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia.

2. 2Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Roma, Italia.

3. 3Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

4. 4Department of Life Sciences and Public Health, Section of Genomic Medicine, Università Cattolica del Sacro Cuore, Roma, Italia.

5. 5Unit of Medical Genetics, Department of Laboratory Science and Infectious Diseases, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia.

6. 6Leibniz Institute for Prevention Research and Epidemiology, BIPS, and University of Bremen, Faculty of Mathematics and Computer Science, Institute of Statistics, Bremen, Germany.

7. 7Cancer Epidemiology Research Programme, IDIBELL, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Spain.

8. 8Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.

9. 9Department of Cardiac Thoracic Vascular Sciences and Public Health, Università di Padova, Padova, Italia.

10. 10Trinity College Dublin School of Dental Science, Dublin, Ireland.

11. 11Institute of Hygiene & Epidemiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.

12. 12Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

13. 13Cancer Epidemiology Unit, Centro di Riferimento Oncologico (CRO) Aviano, IRCCS, Aviano, Italia.

14. 14Cancer Epidemiology Unit, Department of Medical Sciences, Università di Torino, Torino, Italia.

15. 15Cancer Registry of Norway, Oslo, Norway.

16. 16Dipartimento Scienze dell'Invecchiamento, Neurologiche, Ortopediche e della Testa-Collo, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italia.

17. 17Dipartimento Patologia Testa Collo e Organi di Senso, Facoltà Medicina e Chirurgia Università Cattolica Sacro Cuore, Roma, Italia.

18. 18International Agency for Research on Cancer, World Health Organization, Lyon, France.

19. 19Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York.

20. 20Division of Cancer Epidemiology and Prevention, Aichi Cancer Center, Nagoya, Japan.

21. 21Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Abstract

Abstract Background: Identification of screening tests for the detection of head and neck cancer (HNC) at an early stage is an important strategy to improving prognosis. Our objective was to identify plasma circulating miRNAs for the diagnosis of HNC (oral and laryngeal subsites), within a multicenter International Head and Neck Cancer Epidemiology consortium. Methods: A high-throughput screening phase with 754 miRNAs was performed in plasma samples of 88 cases and 88 controls, followed by a validation phase of the differentially expressed miRNAs, identified in the screening, in samples of 396 cases and 396 controls. Comparison of the fold changes (FC) was carried out using the Wilcoxon rank-sum test and the Dunn multiple comparison test. Results: We identified miR-151-3p (FC = 1.73, P = 0.007) as differentially expressed miRNAs in the screening and validation phase. The miR-151-3p was the only overexpressed miRNA in validation sample of patients with HNC with early stage at diagnosis (FC = 1.81, P = 0.008) and it was confirmed upregulated both in smoker early-stage cases (FC = 3.52, P = 0.024) and in nonsmoker early-stage cases (FC = 1.60, P = 0.025) compared with controls. Conclusions: We identified miR-151-3p as an early marker of HNC. This miRNA was the only upregulated in patients at early stages of the disease, independently of the smoking status. Impact: The prognosis for HNC is still poor. The discovery of a new diagnostic biomarker could lead to an earlier tumor discovery and therefore to an improvement in patient prognosis.

Funder

Associazione Italiana per la Ricerca sul Cancro

Fondazione Umberto Veronesi

Università Cattolica del Sacro Cuore

Publisher

American Association for Cancer Research (AACR)

Subject

Oncology,Epidemiology

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