Single-Cell Transcriptomic Landscape of Laryngeal Squamous Cell Carcinoma from Precancerous to Cancerous Lesions

Laryngeal squamous cell carcinoma (LSCC), a significant and aggressive type of head and neck cancer, primarily originates from the precancerous lesions of the larynx. However, the mechanisms driving the progression from laryngeal precancerosis to carcinoma remain unclear. To address this and provide therapeutic candidates, we compile a single-cell transcriptome atlas of the laryngeal precancerous lesion, carcinoma in situ, and squamous cell carcinoma from patient samples. We uncover the complex cellular landscape of these lesions, revealing distinct cell populations and their unique transcriptional profiles at various stages of disease progression. Notably, our analysis identifies a key subtype of epithelial cells in laryngeal precancerosis, characterized by the expression of TOP2A, HMGB2 and PTTG1, linked to aggressive LSCC behavior. Within this TOP2A+HMGB2+PTTG1+subset, polo-like kinase-1 (PLK1) emerged as a pivotal therapeutic target. Further studies demonstrate that a component derived from the Chinese Medicine Compound ReYanNingHeJi, quercetin, effectively target and inhibit PLK1 activity, thereby reducing cellular proliferation. Therefore, this study sheds new light on the understanding of precancerous lesions progression and offers potential candidates for clinical intervention.