Immune expression profile identification in a group of proliferative verrucous leukoplakia patients: a pre-cancer niche for oral squamous cell carcinoma development

Carlos Llorens et al.

Objectives: To explore the pathophysiology of proliferative verrucous leukoplakia, a rare oral disorder that exhibits high rates of recurrence and malignant transformation, through a RNAseq case-control study.

Material and methods: We obtained oral biopsies from 10 patients with verrucous leukoplakia lesions and from the mucosa of 5 healthy individuals for sequencing using RNAseq technology. Using bioinformatic methods, we investigated gene expression and enrichment differences between patients both with and without the disorder. We applied network biology methods to investigate functional relations among those genes that were differentially deregulated.

Results: We detected 140 differentially expressed genes with distinct roles in immune surveillance, tissue and organ morphogenesis, development, and organization. Of these 140 genes, 111 have been previously described as cancer expression biomarkers, being oral squamous cell carcinoma the most represented type of cancer among them. Of these 140 genes, 26 were prioritized for further investigation as biomarkers using larger sample sizes.

Conclusions: The gene expression patterns of healthy and unhealthy patients differed in 140 genes whose deregulation has a functional impact on normal functioning of the immune system. This immune expression profile provides a plausible hypothesis to explain the transformation to oral squamous cell carcinoma observed in 6 of the 10 assayed cases.

Clinical relevance: By determining the molecular bases of the proliferative verrucous leukoplakia disorder and identifying early biomarkers of malignancy, this can allow us to develop new treatment strategies.

Keywords: Differential expression; Fiber organization; Gene ontology; Immune response; Oral squamous cell carcinoma; Proliferative verrucous leukoplakia; Protein-protein interaction networks.

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