Heterogeneous Expression Patterns of the Minichromosome Maintenance Complex Members in Retinoblastoma Unveil its Clinical Significance

Abstract

Purpose : To explore the expression patterns and clinical significance of Minichromosome Maintenance (MCM) complex members in retinoblastoma (RB).

Methods : Single-cell RNA sequencing (scRNA-seq) datasets from 5 normal retina, 6 intraocular, and 5 extraocular RB samples were integrated to characterize the expression patterns of MCM complex members at the single-cell level. Western blot and qPCR were employed to detect the expression of MCM complex members in RB cell lines. Immunohistochemistry was conducted to validate the expression of MCM complex members in RB patient samples and a RB mouse model.

Results : The expression of MCM2-7 is increased in RB tissue, with MCM2/3/7 showing particularly elevated levels in extraocular RB. MCM3/7 are abundantly detected in cell types associated with oncogenesis. Both mRNA and protein levels of MCM3/4/6/7 are increased in RB cell lines. Immunohistochemistry further confirmed the elevated expression of MCM3 in extraocular RB, with MCM6 being the most abundantly expressed MCM in RB.

Conclusions : The distinct MCM expression patterns across various RB cell types suggest diverse functional roles, offering valuable insights for targeted therapeutic strategies. The upregulation of MCM3, MCM4, MCM6, and MCM7 in RB, with a specific emphasis on MCM6 as a notable marker, highlights their potential significance.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Validation of MCM6 Expression in a Murine Retinoblastoma Model. (A) Histopathological and (B) immunohistochemical analyses in a murine model injected with WERI-Rb1 cells, illustrating tumor infiltration and significant expression of MCM6 in tumor tissue compared to non-cancerous tissues.