Usefulness of protein-based salivary markers in the diagnosis of oral potentially malignant disorders: A systematic review and meta-analysis

Article type: Systematic Review

Authors: Arroyo, Esteban^{a; 1} | Donís, Sergio Piñeiro^{b; 1} | Petronacci, Cintia M. Chamorro^{b; c} | Alves, Monica G. Oliveira^{d; e} | Mendía, Xabier Marichalar^f | Fernandes, Darcy^a | Pouso, Alejandro I. Lorenzo^b | Bufalino, Andreia^a | Bravo López, Susana^g | Sayáns, Mario Pérez^{a; b; *}

Affiliations: [a] Department of Diagnosis and Surgery, Araraquara, School of Dentistry, São Paulo State University, Araraquara, SP, Brazil | [b] Oral Medicine, Oral Surgery and Implantology Unit, Faculty of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela, Spain | [c] ORALRES Group, Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain | [d] School of Medicine, Anhembi Morumbi University, São José dos Campos, São Paulo, Brazil | [e] School of Dentistry, University of Mogi das Cruzes, Mogi das Cruzes, São Paulo, Brazil | [f] Department of Stomatology II, School of Medicine and Dentistry, Leioa, Biscay, Spain | [g] Proteomic Unit, Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain

Correspondence: [*] Corresponding author: Mario Pérez-Sayáns, MDS, FDS, DDS, Faculty of Dentistry, Entrerríos s/n, Santiago de Compostela C.P. 15782, Spain. Tel.: +34 626233504; E-mail: [email protected].

Note: [1] These authors contributed equally to this paper study.

Abstract: By using a meta-analytical approach, this study aimed to analyse the diagnostic capacity of protein-based biomarkers in saliva for the differential diagnosis of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) from healthy individuals as control group (HCG). Articles on protein-based biomarkers in saliva, which provided quantitative expression in individuals with clinical and histopathological diagnosis of OPMD or oral leukoplakia (OL) were considered eligible. Searches were conducted in eight electronic databases. The methodological quality was assessed using the Quality Assessment of Diagnostic Studies tool (QUADAS-2). Functional analysis was also performed. Meta-analyses were performed using the OpenMeta tool (Analyst). Meta-analysis was possible for 4 of the 11 biomarkers studied. Only the carcinoembryonic antigen (CEA) and the soluble fragment of cytokeratin 19 (CYFRA21) were significant for the OSCC/OPMD subgroup, both with a very low heterogeneity. CEA had an OE = 25.854 (CI95%: 13.215–38.492, p< 0.001, I2 = 0) and CYFRA21 had an OE = 9.317 (CI95%: 9.014–9.619, p< 0.001, I2 = 0). For the OPMD/HCG subgroup, only CYFRA21 was significant, with an OE = 3.679 (CI95%: 0.663–6.696, p= 0.017) although with high heterogeneity (I2 = 91.24). The CEA and CYFRA21 markers proved very useful when differentiating OSCC from OPMD. The CYFRA21 was the only protein that was capable of distinguishing between OPMD and healthy controls.

Keywords: Systematic review, meta-analysis, protein-based biomarkers, saliva, oral leukoplakia, oral potentially malignant lesions

DOI: 10.3233/CBM-203043

Journal: Cancer Biomarkers, vol. 32, no. 4, pp. 411-424, 2021