| Abstract | Introduction: Vocal fold leukoplakia (VFL) is designated “epithelial hyperplastic laryngeal lesions” . VFL occupy a central position in the oncogenesis of Head and neck squamous cell carcinoma (HNSCC).Cancer-associated fibroblasts are of great significance due to their interactions with cancer cells. However, the relationship between fibroblasts and VFL cell remains uncertain.
Methods: We used single-cell RNA sequencing to characterize the mucosal immune microenvironment of VFL. The main cell types were identified based on gene expression patterns determined using dimensionality reduction and unsupervised cell clustering. Non-negative matrix factorization clustering of the gene expression of fibroblasts from VFL and macrophages was performed. Kyoto Encyclopedia of Genes and Genomes pathway analyses and gene set enrichment analysis were performed to explore significant functional pathways.
Results: We generated a transcriptome atlas from five VFL biopsy samples and compared them with one healthy tissues and four HNSCC samples. To further elucidate the origin and role of fibroblasts from VFL, we analyze single-cell RNA sequencing and identify nine distinct cell types. Then, ten subtypes of fibroblasts are further distinguished. Based on the differentially upregulated genes of fibroblasts,GO enrichment analysis reveals their different roles in VFL progression. Whatsmore, the trajectory order of fibroblast-1 potentially taking part in the transformation from VFL to caner. several molecular pathways, such as IL-17 signaling pathway, TNF signaling pathway and HIF-1 signaling pathway associated with cancer transition were enriched in fibroblast-1.
Conclusions: The results revealed the characteristics of fibroblasts in vocal fold leukoplakia in progression of precancerous lesions at single-cell transcriptome level, providing new insights for inhibit the progression of precancerous lesions.
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