Comprehensive analysis of single-cell and bulk RNA sequencing uncover tumor microenvironment diversity in invasive Retinoblastoma

In this study, we analyzed publicly available scRNA-seq data from primary tumor tissues of 10 Retinoblastoma (RB) patients to explore tumor microenvironment (TME) heterogeneity. Our findings revealed distinct subpopulations of cone precursor (CP) cells, with higher proportions in invasive RB. Differential gene expression and pathway analysis highlighted functional diversity among CP subpopulations, with CP4 showing elevated TGF-β signaling in invasive RB. Cell-cell interaction analysis further identified rewiring of communication networks, with increased fibroblast-CP interactions in invasive tumors. Bulk RNA-seq identified two molecular subtypes, with subtype 1 showing an immunosuppressive TME. Finally, DOK7 was identified as a key gene associated with invasion, with functional assays confirming its role in promoting tumor progression. These results provide valuable insights into RB progression and potential therapeutic targets.