Identification of Proteomic Biomarkers in Proliferative Verrucous Leukoplakia through Liquid Chromatography With Tandem Mass Spectrometry.

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.

Protein-based salivary biomarkers for the diagnosis of periodontal diseases: Systematic review and meta-analysis.

Objective: This systematic review and meta-analysis was aimed at determining differentially expressed protein-based biomarkers detectable in the saliva for the diagnosis of major periodontal diseases. Methods: A literature review was conducted through January 31, 2022. The methodological quality and risk of bias were assessed with the Newcastle-Ottawa scale for case-control studies. Heterogeneity among studies was analysed with the Q statistical test and the I2 test. p-values lower than 0.10 and I2 values higher than 50% indicated high heterogeneity among studies; therefore, the random-effects model was used. The analysis of biological pathways associated with the differentially expressed protein markers was performed with the STITCH integration analysis tool and was limited to interactions with high confidence levels (0.7). Results: Of all protein-based biomarkers detected, 12 were suitable for meta-analysis: IL-1ß, MIP-1α, albumin, TNF-α, ICTP, Ig-A, lactoferrin, MMP-8, IL-6, IL-8, IL-17 and PGE2. The salivary markers with high applicability were IL-1ß for differentiating patients with chronic periodontal disease from patients with gingivitis with an OE = 73.5 pg/mL; ICTP for differentiating patients with chronic periodontal disease from healthy control patients with an OE = 0.091 ng/mL; and PGE2 for differentiating patients with chronic periodontal disease from healthy control patients with an OE = 36.3 pg/mL. Conclusions: The biomarkers with the highest differential expression and the greatest potential for clinical applicability are IL-1ß for differentiating periodontitis from gingivitis, and ICTP and PGE2 for differentiating periodontitis from healthy status.

Overexpression of E-Cadherin Is a Favorable Prognostic Biomarker in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Oral squamous cell carcinoma (OSCC) is characterized by poor survival, mostly due to local invasion, loco-regional recurrence, and metastasis. Given that the weakening of cell-to-cell adhesion is a feature associated with the migration and invasion of cancer cells, different studies have explored the prognostic utility of cell adhesion molecules such as E-cadherin (E-cad). This study aims to summarize current evidence in a meta-analysis, focusing on the prognostic role of E-cad in OSCC. To find studies meeting inclusion criteria, Scopus, Web of Science, EMBASE, Medline, and OpenGrey databases were systematically assessed and screened. The selection process led to 25 studies, which were considered eligible for inclusion in the meta-analysis, representing a sample of 2553 patients. E-cad overexpression was strongly associated with longer overall survival (OS) with Hazard Ratio (HR) = 0.41 95% confidence interval (95% CI) (0.32-0.54); p < 0.001 and disease-free survival with HR 0.47 95% CI (0.37-0.61); p < 0.001. In terms of OS, patients with tongue cancer experienced better survivability when expressing E-cad with HR 0.28 95% CI (0.19-0.43); p < 0.001. Globally, our findings indicate the prognostic role of the immunohistochemical assessment of E-cad in OSCC and its expression might acquire a different role based on the oral cavity subsites.

Multicentre retrospective study of 97 cases of intraoral lipoma.

BACKGROUND: Lipomas are benign neoplasms derived from adipose tissue that are unfrequently found in the oral cavity. The objective of this study is to identify the main clinicopathological characteristics of this tumour in a case series of oral lipomas (OL) in a population from Spain and Brazil. MATERIAL AND METHODS: A multicentre retrospective observational study was conducted in collaboration with the Oral Pathology Unit of the São Paulo State University (UNESP), São José dos Campos, in Brazil, and the Oral Medicine and Pathology Units of the University of Santiago de Compostela (USC) and the University of the Basque Country (UPV/EHU) in Spain. RESULTS: This multicentre series consists of a total of 97 of OL cases, 31 (32%) of which correspond to Spain, and 66 (68%) to Brazil with an overall prevalence of 0.33%. The average age of the patients is 56.44 years old, with a range of 10-92 (SD = 15.52). Buccal mucosa was the most frequent location (42.3%). Cases from Spain coexisted with other lesions in a significant number of cases, 12.9%, vs Brazil, 1.5% (P = 0.018). According to the progression time, Brazil has an average of 60.35 months (CI: 27.20-93.51), compared to 5.41 months in Spain (CI: 3.17-7.65) (P = 0.022). Average size is 12.55 mm (SD = 11.06), ranging from 2 to 75 mm. A positive correlation is also seen between the increase in the lesion size and a greater progression time (CC = 0.367; P = 0.008). CONCLUSIONS: Correct differential diagnosis of the clinical lesion is key, followed by a good histopathological study, to achieve the final diagnosis.