Abstract
Purpose :
Retinoblastoma (RB) is the most prevalent ocular tumor of childhood whose extraocular invasion largely increase metastasis risk. Nevertheless, a single-cell characterization of RB local extension has been lacking. Our study aim to comprehensively profile cellular and molecular signatures giving rise to local invasion process in RB.
Methods :
Here, we perform single-cell RNA sequencing (scRNA-seq) on 4 RB samples (2 from intraocular and 2 from extraocular RB patients), and integrate public scRNA-seq datasets of 5 normal retina, 4 intraocular, and 3 extraocular RB samples to characterize the local extension of RB at single-cell level.
Results :
A total of 128,454 qualified cells were obtained in 9 major cell types. Copy number variation (CNV) inference reveals chromosome 6p amplification in cells derived from extraocular RB samples and positive correlations between expression level and copy number of genes on 6p22 were observed. In cellular heterogeneity analysis, we identified 10, 8, and 7 cell subpopulations in cone precursor like (CPL) cells, retinoma like (RL) cells, and MKI67+ photoreceptorness decreased (MKI67+ PhrD) cells, respectively. Compared with intraocular RB, low photoreceptor signature expression was identified in extraocular RB, reflecting tumor progression by a gradual loss of differentiation. High expression level of SOX4 was detected in cells from extraocular RB samples, especially in MKI67+ PhrD cells, which was verified on additional clinical RB samples. These results suggest that SOX4 might drive RB local extension.
Conclusions :
Our study presents a single-cell transcriptomic landscape of intraocular and extraocular RB samples, which improves our understanding of RB local extension at single-cell resolution and provides potential therapeutic targets for RB patients.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.