Immune Cell-Mediated Retinoblastoma Development: Genetic and Molecular Mechanisms

Retinoblastoma (RB) is the most prevalent malignant tumor that originates within the eye in children, occurring at a frequency of around 1:20,000 to 1:15,000. RB typically occurs when both alleles of the retinoblastoma 1 (RB1) gene are deactivated. RB is associated with variations in the tumor suppressor gene RB1 and is inherited in an autosomal recessive manner, operating at the genetic level. Variation in RB1 occurs only when two alleles of the RB1 gene are mutated. The mechanism by which immune cells mediate RB1 to affect RB is still unclear. Using two-sample Mendelian randomization (MR) analysis based on published genome-wide association study (GWAS) summary statistics, we investigated the relationship between immune cells and RB1 proteins. Our goal was to understand their potential role in the development of RB in offspring. The analysis of alterations in RB tissue cells and potential molecular mechanisms was conducted using single-cell RNA sequencing data. The research revealed the presence of 28 immune cells linked with RB1. These variables might potentially impact the likelihood of RB in children by altering the expression of the RB1 gene in their parents. Furthermore, we found differential gene expression in different cells of the RB tissue. EZH2, UBLCP1, and HKDC1 overlapped with the identified instrumental variables (IVs) of immune cells to investigate potential molecular mechanisms by which immune cells participate in RB processes.