A Meta-analysis Reveals the Protein Profile Associated with Malignant Transformation of Oral Leukoplakia

Overview

Journal Front Oral Health

Date 2023 Mar 16

PMID 36923449

Authors

Ana Gabriela Costa Normando

Erison Santana Dos Santos

Jamile de Oliveira Sa

Ariane Fidelis Busso-Lopes

Tatiane De Rossi

Fabio Malta de Sa Patroni

Daniela Campos Granato

Eliete Neves Silva Guerra

Alan Roger Santos-Silva

Marcio Ajudarte Lopes

Adriana Franco Paes Leme

Affiliations

Soon will be listed here.

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.

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