A1 Refereed original research article in a scientific journal
Identification of Proteomic Biomarkers in Proliferative Verrucous Leukoplakia through Liquid Chromatography With Tandem Mass Spectrometry
Authors: Arroyo E, Pérez Sayáns M, Bravo SB, de Oliveira Barbeiro C, Paravani Palaçon M, Chamorro Petronacci CM, García Vence M, Chantada Vázquez MDP, Blanco Carrión A, Suárez Peñaranda JM, García García A, Gándara Vila P, Días Almeida J, Veríssimo da Costa GC, Sousa Nogueira FC, Medeiros Evaristo JA, de Abreu Pereira D, Rintala M, Salo T, Rautava J, Padín Iruegas E, Oliveira Alves MG, Morandin Ferrisse T, Albergoni da Silveira H, Esquiche León J, Vilela Silva E, Flores IL, Bufalino A
Publisher: Elsevier BV
Publication year: 2023
Journal: Laboratory Investigation
Journal name in source: Laboratory investigation; a journal of technical methods and pathology
Journal acronym: Lab Invest
Article number: 100222
Volume: 103
Issue: 10
ISSN: 0023-6837
eISSN: 1530-0307
DOI: https://doi.org/10.1016/j.labinv.2023.100222
Web address : https://doi.org/10.1016/j.labinv.2023.100222
Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder associated with high risk of malignant transformation. Currently, there is no treatment available, and restrictive follow-up of patients is crucial for a better prognosis. Oral leukoplakia (OL) shares some clinical and microscopic features with PVL but exhibits different clinical manifestations and a lower rate of malignant transformation. This study aimed to investigate the proteomic profile of PVL in tissue and saliva samples to identify potential diagnostic biomarkers with therapeutic implications. Tissue and saliva samples obtained from patients with PVL were compared with those from patients with oral OL and controls. Label-free liquid chromatography with tandem mass spectrometry was employed, followed by qualitative and quantitative analyses, to identify differentially expressed proteins. Potential biomarkers were identified and further validated using immunohistochemistry. Staining intensity scan analyses were performed on tissue samples from patients with PVL, patients with OL, and controls from Brazil, Spain, and Finland. The study revealed differences in the immune system, cell cycle, DNA regulation, apoptosis pathways, and the whole proteome of PVL samples. In addition, liquid chromatography with tandem mass spectrometry analyses showed that calreticulin (CALR), receptor of activated protein C kinase 1 (RACK1), and 14-3-3 Tau-protein (YWHAQ) were highly expressed in PVL samples. Immunohistochemistry validation confirmed increased CARL expression in PVL compared with OL. Conversely, RACK1 and YWHA were highly expressed in oral potentially malignant disorder compared to the control group. Furthermore, significant differences in CALR and RACK1 expression were observed in the OL group when comparing samples with and without oral epithelial dysplasia, unlike the PVL. This research provides insights into the molecular mechanisms underlying these conditions and highlights potential targets for future diagnostic and therapeutic approaches.
