Spatial Proteomic Analysis Highlights Molecular Reprogramming in Optic Nerve Invasive Retinoblastoma

Area of Science:

• Oncology
• Molecular Biology
• Cancer Metastasis

Background:

• Molecular reprogramming drives cancer heterogeneity and metastasis.
• Optic nerve metastasis in retinoblastoma (RB) is a critical indicator of poor prognosis.
• Understanding the molecular basis of RB optic nerve invasion is crucial for improving patient outcomes.

Purpose of the Study:

• To investigate the molecular mechanisms underlying retinoblastoma (RB) optic nerve invasion (ONI).
• To delineate the spatial proteomic heterogeneity in RB with ONI.
• To identify molecular reprogramming events at the tumor boundary associated with metastasis.

Main Methods:

• Spatial proteomic analysis of three RB samples with ONI, comparing invasive and intraretinal regions, and tumor center versus boundary.
• Immunofluorescence validation of key protein expression in additional RB samples.
• Data archiving and public accessibility via Mendeley Data.

Main Results:

• Significant alterations in cholesterol metabolism were observed in optic nerve-invasive RB lesions.
• Tumor boundaries showed upregulated anaplerotic reactions, oxidative respiration, and keratin-mediated cytoskeletal remodeling.
• Epigenetic remodeling, including decreased KMT5C (lysine methyltransferase 5C), was identified at invasive boundaries, impacting epithelial/mesenchymal transition.

Conclusions:

• This study provides the first spatial proteomic landscape of retinoblastoma with optic nerve invasion.
• Identified molecular reprogramming events at the tumor boundary are critical for understanding RB metastasis.
• Findings highlight potential therapeutic targets related to metabolic and epigenetic alterations in RB ONI.