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.

Proliferative verrucous leukoplakia and its tumor markers: Systematic review and meta-analysis.

BACKGROUND: The aim was to update information on oral proliferative verrucous leukoplakia (PVL), a disease of verrucous-like lesions with high risk of malignancy, and its biomarkers. METHODS: A systematic search of literature on PVL and its biomarkers showed 22 biomarkers that were investigated in 19 papers. A meta-analysis was possible for human papillomavirus (HPV), aneuploidy, Ki-67, and p53. RESULTS: Aneuploidy was found consistently (I2 = 0%, P = 0.61) in 92% (95% CI 80%-99%) of the PVL cases. P53 positivity prevalence was 27% (95% CI 15%-40%) in two available studies (I2 = 0%, P = 0.64). With HPV and Ki-67, the most outlying studies needed to be removed and after that the pooled HPV positivity prevalence (I2 = 24%, P = 0.27) was 5% (95% CI 0%-14%) and for Ki-67 (I2 = 9%, P = 0.33) 14% (95% CI 6%-26%). CONCLUSIONS: With the evidence of the current literature, aneuploidy could value as a biomarker of PVL but should be further validated.