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

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Normando, Ana Gabriela Costa ; dos Santos, Erison Santana ; Sa, Jamile de Oliveira ; Busso-Lopes, Ariane Fidelis ; De Rossi, Tatiane ; Patroni, Fabio Malta de Sa ; Granato, Daniela Campos ; Guerra, Eliete Neves Silva ; Santos-Silva, Alan Roger ; Lopes, Marcio Ajudarte ; Leme, Adriana Franco Paes

• Document type: Journal article
• Source: FRONTIERS IN ORAL HEALTH; v. 4, p. 15-pg., 2023-02-27.

Abstract

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. (AU)

• FAPESP's process: 22/04490-1 - Validation of markers of malignant transformation into oral squamous cell carcinoma using imaging mass cytometry and targeted proteomics
• Grantee: Erison Santana dos Santos
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/18751-9 - Discovery and validation of prognostic candidates for oral cancer in liquid biopsies.
• Grantee: Daniela Campos Granato
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 21/03319-4 - Characterization of the role of tumor extracellular vesicles in tolerant tumor microenvironment through TCD4 lymphocyte modulation in oral carcinoma
• Grantee: Tatiane de Rossi Mazo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/09692-9 - Validation of target proteins associated with the progression of potentially malignant disorders into Oral Cancer
• Grantee: Ana Gabriela Costa Normando
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/15535-0 - From discovery to validation of prognostic candidates for oral cancer in liquid biopsies
• Grantee: Daniela Campos Granato
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 21/05965-0 - Study of extracellular vesicles in the initiation of immune response by dendritic cells and T lymphocytes
• Grantee: Jamile de Oliveira Sá
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/18496-6 - The role of alcohol treated-extracellular vesicles in oral cells transformation
• Grantee: Adriana Franco Paes Leme
• Support Opportunities: Research Projects - Thematic Grants