# Descriptive transcriptomic profiling differentiates oral leukoplakia from proliferative verrucous leukoplakia and reveals distinct molecular signatures

## TL;DR

This study uses transcriptomic profiling to distinguish between two oral disorders and identifies potential biomarkers for diagnosis and prognosis.

## Contribution

The study reveals distinct molecular signatures and potential biomarkers in proliferative verrucous leukoplakia through transcriptomic profiling.

## Key findings

- Overexpressed genes in proliferative verrucous leukoplakia are linked to inflammation and immune regulation.
- Syndecan 3 gene variants are identified as potential biomarkers for diagnosis and prognosis in proliferative verrucous leukoplakia.
- Distinct miRNA profiles, including MIR1246 and MIR767 overexpression, are observed in proliferative verrucous leukoplakia.

## Abstract

Oral leukoplakia and proliferative verrucous leukoplakia represent oral potentially malignant disorders. Oral leukoplakia typically presents as solitary lesions, while proliferative verrucous leukoplakia manifests as multifocal lesions with higher malignant potential. This study aimed to investigate the genetic heterogeneity between these disorders through differential gene expression, genetic variants, and microRNA profiling to identify potential biomarkers for diagnosis and prognosis.

Biopsies and peripheral blood samples were obtained from 20 patients. Subsequently, RNA extraction, RNA-Seq libraries preparation, and bioinformatic analyses were conducted to ascertain differential gene expression, genetic variants, and microRNA expression.

In mRNA analysis, overexpressed genes in proliferative verrucous leukoplakia are primarily associated with inflammation and immune regulation, while underexpressed genes relate to skin barrier maintenance. Pathway analysis reveals underexpressed genes related to impaired keratinization in proliferative verrucous leukoplakia and with keratin envelope formation in oral leukoplakia, while overexpressed genes are linked to synaptic processes and protein-protein interactions. Somatic mutation drivers in proliferative verrucous leukoplakia include variants in NRXN3, SRGAP2B, INIP, MYO18A, and ATF7IP genes. Regarding variant analysis, two variants in the Syndecan 3 (SDC3) gene identified in proliferative verrucous leukoplakia have demonstrated enormous value and indicate an important biomarker for a differential diagnosis and to predict prognosis. Proliferative verrucous leukoplakia shows in miRNA analysis MIR1246 and MIR767 overexpression, with MIR135B being the most underexpressed.

Our findings emphasize the intricate transcriptomic profiles in oral leukoplakia and proliferative verrucous leukoplakia development, laying the groundwork for future studies to enhance clinical management and patient outcomes in oral oncology. Syndecan 3 gene polymorphisms may represent a key point in proliferative verrucous leukoplakia differential diagnosis and prognostic prediction.