Abstract
Background: Head and neck squamous cell carcinoma (HNSC) is a globally prevalent malignancy with high mortality rates. RNA-binding proteins (RBPs) are crucial regulators of gene expression and play significant roles in cancer development. However, a comprehensive understanding of RBPs at the single-cell level in HNSC remains limited.ObjectiveThis study aims to investigate the role of RBPs in the stepwise progression of HNSC at the single-cell level, focusing on their expression patterns, prognostic potential, and involvement in key signaling pathways.MethodsWe analyzed single-cell RNA-sequencing data from HNSC samples across four stages, from normal tissue to precancerous leukoplakia, then to primary cancer and finally to metastatic tumors, examining the expression of 2141 previously reported RBPs. We identified RBP-based cell clusters and explored their associations with disease stages, cell types, and cancer progression. A prognostic risk model was developed based on RBPs with significant relevance to patient outcomes.ResultsRBPs displayed distinct cell type-specific expression patterns across different stages of HNSC. We found a significant correlation between RBP-based cell clusters and cancer progression. Notably, a prognostic model was constructed using RBPs such as CELF2, which showed downregulation from early leukoplakia to advanced cancer stages. Fibroblast RBPs were dynamically regulated, particularly in extracellular matrix remodeling, with key proteins like CFL1 and PFN1 linked to improved prognosis. Furthermore, we identified heterogeneity in RBP regulation of the Macrophage Migration Inhibitory Factor (MIF) signaling pathway across cell types during the precancerous stage.ConclusionsOur findings highlight the crucial roles of RBPs in HNSC progression and suggest their potential as therapeutic targets and prognostic markers, offering insights into personalized treatment strategies.