Proteomic analysis of oral squamous cell carcinoma affecting young patients reveals potential therapeutic targets for HPV-related tumors: preliminary results

Presentation: C021
Topic: Oral Cancer
Type: Poster
Date: Thursday, April 19, 2018
Session: 9:00 AM - 7:00 PM
Authors: Marisol Miranda Galvis1, Carolina Carneiro Soares1, Carolina Moretto Carnielli2, Fabio Albuquerque Marchi3, Alan Santos-Silva1, Adriana Paes Leme2, Estela Kaminagakura4, Clóvis A. Lópes Pinto5, Luiz P Kowalski6
Institution(s): 1Oral Diagnosis Department, Piracicaba Dental School, University of Campinas (UNICAMP), Piracicaba, Brazil, 2Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas, São Paulo, Brazil., 3International Research Center (CIPE), A.C.Camargo Cancer Center, São Paulo, Brazil., 4Departament of Bioscience and Oral Diagnosis, Science and Technology Institute, Univ Estadual Paulista (UNESP), São José dos Campos, Brazil., 5Department of Anatomic Pathology, A.C.Camargo Cancer Center, São Paulo, Brazil., 6Department of Head and Neck Surgery and Otorhinolaryngology, A.C.Camargo Cancer Center, São Paulo, Brazil.

Introduction: Although the prevalence of oral squamous cell carcinoma (OSCC) has increased worldwide in young patients, there is no consensus regarding its etiological factors. Nevertheless, previous studies have proposed that high-risk human papillomavirus (HR-HPV) may be a promoting agent of oral carcinogenesis in this age group.

Aim: Compare the total proteome profile of HR-HPV positive (HR-HPV+) and HR-HPV negative (HR-HPV-) OSCC samples from young patients to identify potential therapeutic targets.

Methods: Laser-capture microdissection was carried out in histological sections obtained from paraffin-embedded surgical specimens from twenty OSCC affecting young patients (≤40 years) and the analysis was performed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Survival probability was calculated based on the Kaplan-Meier method and relative risk was evaluated by the Cox proportional hazards model. miRNA prediction was performed using miRWalk 2.0 considering at least 3 databases in target selection.

Results: A total of 1,030 proteins were identified and 26 were differentially expressed and enriched for biological processes in HR-HPV+ and HR-HPV- tumors. Thirteen proteins were down-regulated and 13 were up-regulated in HR-HPV+ OSCC. A2M (Alpha-2-macroglobulin), COPS3 (COP9 signalosome complex subunit 3), S100A8 (Protein S100-A8), and SERPINA1 (Alpha-1-antitrypsin) were associated with a lower disease-free survival (p = 0.001, p = 0.011, p = 0.001 and p = 0.001, respectively) in univariate and multivariate analysis. Furthermore, miRNA prediction revealed that the above mentioned proteins are correlated with miRNAs as possible regulatory mechanisms in OSCC development (Fold change: 1.85, 1.97, 2.40, 1.74, respectively).

Conclusions: HR-HPV infection may be an independent etiologic factor for OSCC in young patients. Moreover, A2M, COPS3, S100A8 and SERPINA1 might represent potential diagnostic and therapeutic targets for HR-HPV-related OSCC. Further validation and functional analysis is ongoing.

Acknowledgments: This work was supported by FAPESP grants: 2016/03248-1. We acknowledge the Mass Spectrometry Laboratory at Brazilian Biosciences National Laboratory, CNPEM, Campinas, Brazil for their support with the mass spectrometry analysis.