Integrating single-cell sequencing and clinical insights to explore malignant transformation in odontogenic keratocyst
Keratocyst
Malignant Transformation
DOI:
10.1016/j.csbj.2025.03.027
Publication Date:
2025-03-18T17:36:30Z
AUTHORS (10)
ABSTRACT
The malignant transformation of odontogenic keratocysts (OKC) into cancerous (COKC) is exceedingly rare, and its mechanisms remain poorly understood. Studies exploring the cellular heterogeneity, molecular pathways, clinical features COKC are limited. In this study, we performed single-cell RNA sequencing (scRNA-seq) on three samples integrated data with a public OKC dataset, identifying 22,509 single cells. Two COKC-specific epithelial subpopulations, Basal-C0-EXT1 Basal-C3-HIST1H3B, were identified. These subpopulations exhibited enhanced stemness invasive potential, respectively, suggesting their roles as key drivers carcinogenesis. Fibroblasts underwent phenotypic transitions, particularly from inflammation-associated fibroblasts (IFBs) to myofibroblasts (MFBs). Similarly, macrophage may also play role in Clinical observations severe lesion-area pain patients suggest potential neuroinvasiveness, Supported by transcriptomic data, imaging findings, histopathological evidence. A review revealed that none cervical lymph node metastasis. Single-cell transcriptomics suggests phenomenon be associated an active immune microenvironment COKC, reduced epithelial-mesenchymal transition (EMT) activity, lower VEGFC expression, upregulated MAST4 expression regulator lymphatic conclusion, exhibits distinct molecular, cellular, characteristics compared OKC, featuring potent neuroinvasiveness low metastatic potential. findings provide important insights underlying development guide novel diagnostic therapeutic strategies.
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