Single-cell transcriptomics dissects premalignant progression in proliferative verrucous leukoplakia.

Area of Science:

• Oral pathology
• Cancer biology
• Single-cell genomics

Background:

• Proliferative verrucous leukoplakia (PVL) presents diverse clinicopathological features.
• PVL carries a significant risk of malignant transformation into oral cancer.

Purpose of the Study:

• To map molecular signature dynamics during PVL progression.
• To identify cell subtypes crucial for PVL's premalignant evolution.

Main Methods:

• Single-cell RNA sequencing was applied to three PVL biopsy samples.
• Samples represented a histopathological continuum of PVL progression.

Main Results:

• Analysis of 27,611 cells identified ten major cell lineages and cellular remodeling.
• Epithelial cells shifted towards tumorigenic and secretory states; immune cells became more immunosuppressive.
• Novel INSR+ endothelial cells and ASPN+ fibroblasts were discovered, potentially driving angiogenesis and fibrosis.

Conclusions:

• This is the first study to detail the PVL cellular landscape.
• Disease progression is likely driven by functional remodeling across multiple cell subtypes.