Pleomorphic adenoma and carcinoma ex‐pleomorphic adenoma tumorigenesis: A proteomic analysis

Author:

Zanella Virgílio Gonzales12ORCID,Costa Sara Ferreira Dos Santos3ORCID,Schuch Lauren Frenzel4ORCID,Pilar Emily Ferreira Salles5ORCID,Paes Leme Adriana Franco4ORCID,dos Santos Jean Nunes6ORCID,Khurram Syed Ali7ORCID,Elalawy Fatima7,Bingle Lynne7ORCID,Nunes Fabio Daumas8ORCID,Fonseca Felipe Paiva34ORCID,Vargas Pablo Agustin4ORCID,Martins Manoela Domingues14ORCID,Wagner Vivian Petersen478ORCID

Affiliation:

1. Department of Pathology, School of Dentistry Federal University of Rio Grande do Sul Porto Alegre Brazil

2. Head and Neck Surgery Department Santa Rita Hospital, Santa Casa de Misericórdia de Porto Alegre Porto Alegre Brazil

3. Department of Oral Surgery and Pathology, School of Dentistry Federal University of Minas Gerais Belo Horizonte Brazil

4. Department of Oral Diagnosis, Piracicaba Dental School University of Campinas Piracicaba Brazil

5. Experimental Research Unit Hospital de Clínicas Porto Alegre Porto Alegre Brazil

6. Postgraduation Program in Dentistry and Health Federal University of Bahia Salvador Brazil

7. Academic Unit of Oral and Maxillofacial Medicine and Pathology, Department of Clinical Dentistry University of Sheffield Sheffield UK

8. Department of Oral and Maxillofacial Pathology, Dental School University of São Paulo (USP) São Paulo Brazil

Abstract

AbstractObjectivesTo conduct a comprehensive proteomic analysis of normal salivary gland tissue, pleomorphic adenoma (PA), and carcinoma ex‐pleomorphic adenoma (CXPA), and validate the proteomic findings using immunohistochemistry.MethodsSix normal salivary gland tissues, seven PA and seven CXPA samples underwent laser microdissection followed by liquid chromatography coupled to mass spectrometry. Protein identification and quantification were performed using MaxQuant software. Statistical analysis and functional enrichment were conducted using the Perseus platform and STRING tool, respectively. Immunohistochemistry was used for validation.ResultsComparative proteomic analysis revealed 2680 proteins across the three tissue types, with 799 significantly altered between groups. Translocation protein SEC63 homolog, Annexin A6 and Biglycan were up‐regulated in CXPA compared to PA. Decorin was markedly up‐regulated in both PA and CXPA compared to normal salivary gland (log2 fold changes of 7.58 and 7.38, respectively). Validation confirmed elevated levels of Biglycan and Decorin in the extracellular matrix of CXPA compared to PA.ConclusionsProteomic analysis identified differential protein expression patterns associated with malignant transformation of PA into CXPA. Findings indicate a crucial role for extracellular matrix proteins, specifically Biglycan and Decorin, in the tumorigenic progression of PA and CXPA.

Funder

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Hospital de Clínicas de Porto Alegre

Fundação de Amparo à Pesquisa do Estado de Minas Gerais

Publisher

Wiley

Reference40 articles.

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3. Pleomorphic adenoma of the parotid gland 1985‐2010: A Danish nationwide study of incidence, recurrence rate and malignant transformation;Andreasen S.;Head & Neck,2016

4. QuPath: Open‐source software for digital pathology image analysis;Bankhead P.;Scientific Reports,2017

5. Combining discovery and targeted proteomics reveals a prognostic signature in oral cancer;Carnielli C. M.;Nature Communications,2018

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