A meta-analysis reveals the protein profile associated with malignant transformation of oral leukoplakia

The search for biomarkers associated with oral leukoplakia malignant transformation is critical for early diagnosis and improved prognosis of oral cancer patients. This systematic review and meta-analysis aimed to assess protein-based markers potentially associated with malignant transformation of o...

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Main Authors: Ana Gabriela Costa Normando, Erison Santana dos Santos, Jamile de Oliveira Sá, Ariane Fidelis Busso-Lopes, Tatiane De Rossi, Fábio Malta de Sá Patroni, Daniela Campos Granato, Eliete Neves Silva Guerra, Alan Roger Santos-Silva, Márcio Ajudarte Lopes, Adriana Franco Paes Leme
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Oral Health
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Online Access:https://www.frontiersin.org/articles/10.3389/froh.2023.1088022/full
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author Ana Gabriela Costa Normando
Ana Gabriela Costa Normando
Erison Santana dos Santos
Erison Santana dos Santos
Jamile de Oliveira Sá
Ariane Fidelis Busso-Lopes
Tatiane De Rossi
Fábio Malta de Sá Patroni
Daniela Campos Granato
Eliete Neves Silva Guerra
Alan Roger Santos-Silva
Márcio Ajudarte Lopes
Adriana Franco Paes Leme
author_facet Ana Gabriela Costa Normando
Ana Gabriela Costa Normando
Erison Santana dos Santos
Erison Santana dos Santos
Jamile de Oliveira Sá
Ariane Fidelis Busso-Lopes
Tatiane De Rossi
Fábio Malta de Sá Patroni
Daniela Campos Granato
Eliete Neves Silva Guerra
Alan Roger Santos-Silva
Márcio Ajudarte Lopes
Adriana Franco Paes Leme
author_sort Ana Gabriela Costa Normando
collection DOAJ
description The search for biomarkers associated with oral leukoplakia malignant transformation is critical for early diagnosis and improved prognosis of oral cancer patients. This systematic review and meta-analysis aimed to assess protein-based markers potentially associated with malignant transformation of oral leukoplakia. Five database and the grey literature were searched. In total, 142 studies were included for qualitative synthesis, where 173 proteins were investigated due to their potential role in malignant progression from oral leukoplakia (OL) to oral squamous cell carcinoma (OSCC). The abundance of these proteins was analyzed in fixed tissues and/or biofluid samples, mainly by immunohistochemistry and ELISA, and 12 were shared by both samples. Enrichment analysis revealed that the differential abundant proteins are mostly involved with regulation of cell death, regulation of cell proliferation, and regulation of apoptotic process. Also, these proteins are mainly expressed in the extracellular region (55.5%), cell surface (24.8%), and vesicles (49.1%). The meta-analysis revealed that the proteins related to tumor progression, PD-L1, Mdm2, and Mucin-4 were significantly associated with greater abundance in OSCC patients, with an Odds Ratio (OR) of 0.12 (95% CI: 0.04–0.40), 0.44 (95% CI: 0.24–0.81), and 0.18 (95% CI: 0.04–0.86), respectively, with a moderate certainty of evidence. The results indicate a set of proteins that have been investigated across OSCC initiation and progression, and whose transcriptional expression is associated with clinical characteristics relevant to the prognosis and aggressiveness. Further verification and validation of this biomarkers set are strongly recommended for future clinical application.
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spelling doaj.art-155503e9334d4dd6a1d0dad06cd8c5b62023-02-27T06:08:03ZengFrontiers Media S.A.Frontiers in Oral Health2673-48422023-02-01410.3389/froh.2023.10880221088022A meta-analysis reveals the protein profile associated with malignant transformation of oral leukoplakiaAna Gabriela Costa Normando0Ana Gabriela Costa Normando1Erison Santana dos Santos2Erison Santana dos Santos3Jamile de Oliveira Sá4Ariane Fidelis Busso-Lopes5Tatiane De Rossi6Fábio Malta de Sá Patroni7Daniela Campos Granato8Eliete Neves Silva Guerra9Alan Roger Santos-Silva10Márcio Ajudarte Lopes11Adriana Franco Paes Leme12Oral Diagnosis Department, Piracicaba Dental School, University of Campinas, Piracicaba, BrazilBrazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, BrazilOral Diagnosis Department, Piracicaba Dental School, University of Campinas, Piracicaba, BrazilBrazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, BrazilBrazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, BrazilBrazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, BrazilBrazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, BrazilMolecular Biology and Genetic Engineering Center, University of Campinas, Campinas, BrazilBrazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, BrazilLaboratory of Oral Histopathology, Health Sciences Faculty, University of Brasilia, Brasilia, BrazilOral Diagnosis Department, Piracicaba Dental School, University of Campinas, Piracicaba, BrazilOral Diagnosis Department, Piracicaba Dental School, University of Campinas, Piracicaba, BrazilBrazilian Biosciences National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, BrazilThe search for biomarkers associated with oral leukoplakia malignant transformation is critical for early diagnosis and improved prognosis of oral cancer patients. This systematic review and meta-analysis aimed to assess protein-based markers potentially associated with malignant transformation of oral leukoplakia. Five database and the grey literature were searched. In total, 142 studies were included for qualitative synthesis, where 173 proteins were investigated due to their potential role in malignant progression from oral leukoplakia (OL) to oral squamous cell carcinoma (OSCC). The abundance of these proteins was analyzed in fixed tissues and/or biofluid samples, mainly by immunohistochemistry and ELISA, and 12 were shared by both samples. Enrichment analysis revealed that the differential abundant proteins are mostly involved with regulation of cell death, regulation of cell proliferation, and regulation of apoptotic process. Also, these proteins are mainly expressed in the extracellular region (55.5%), cell surface (24.8%), and vesicles (49.1%). The meta-analysis revealed that the proteins related to tumor progression, PD-L1, Mdm2, and Mucin-4 were significantly associated with greater abundance in OSCC patients, with an Odds Ratio (OR) of 0.12 (95% CI: 0.04–0.40), 0.44 (95% CI: 0.24–0.81), and 0.18 (95% CI: 0.04–0.86), respectively, with a moderate certainty of evidence. The results indicate a set of proteins that have been investigated across OSCC initiation and progression, and whose transcriptional expression is associated with clinical characteristics relevant to the prognosis and aggressiveness. Further verification and validation of this biomarkers set are strongly recommended for future clinical application.https://www.frontiersin.org/articles/10.3389/froh.2023.1088022/fulloral canceroral leukoplakiamalignant transformationproteinssystematic reviewmeta-analysis
spellingShingle Ana Gabriela Costa Normando
Ana Gabriela Costa Normando
Erison Santana dos Santos
Erison Santana dos Santos
Jamile de Oliveira Sá
Ariane Fidelis Busso-Lopes
Tatiane De Rossi
Fábio Malta de Sá Patroni
Daniela Campos Granato
Eliete Neves Silva Guerra
Alan Roger Santos-Silva
Márcio Ajudarte Lopes
Adriana Franco Paes Leme
A meta-analysis reveals the protein profile associated with malignant transformation of oral leukoplakia
Frontiers in Oral Health
oral cancer
oral leukoplakia
malignant transformation
proteins
systematic review
meta-analysis
title A meta-analysis reveals the protein profile associated with malignant transformation of oral leukoplakia
title_full A meta-analysis reveals the protein profile associated with malignant transformation of oral leukoplakia
title_fullStr A meta-analysis reveals the protein profile associated with malignant transformation of oral leukoplakia
title_full_unstemmed A meta-analysis reveals the protein profile associated with malignant transformation of oral leukoplakia
title_short A meta-analysis reveals the protein profile associated with malignant transformation of oral leukoplakia
title_sort meta analysis reveals the protein profile associated with malignant transformation of oral leukoplakia
topic oral cancer
oral leukoplakia
malignant transformation
proteins
systematic review
meta-analysis
url https://www.frontiersin.org/articles/10.3389/froh.2023.1088022/full
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