Modeled Aqueous Humor Protein Concentrations to Enable Biomarker Development in Uveal Melanoma

Area of Science:

• Ophthalmology
• Oncology
• Proteomics

Background:

• Uveal melanoma (UM) lacks reliable biomarkers for risk stratification, necessitating alternatives to invasive tumor biopsy.
• Molecular profiling of aqueous humor (AH) presents a promising, minimally invasive approach for biomarker discovery.

Purpose of the Study:

• To create a calibrated AH protein map for identifying tumor-associated signals.
• To assess the association of these proteins with UM molecular and clinical features.

Main Methods:

• Analysis of AH samples from 70 UM patients using next-generation sequencing-based proximity extension assays (PEAs).
• Quantification of protein concentrations in picograms per milliliter (pg/mL) using regression models and qPCR-based PEA.
• Examination of 23 proteins with concentrations above 5 pg/mL for clinical relevance.

Main Results:

• Several proteins (e.g., CXCL8, VEGFA, PDCD1) showed increased levels in higher-grade UM and advanced stages (AJCC Stage III/IV).
• Proteomic analysis revealed activated inflammatory and tumor microenvironment pathways.
• VEGFA and CCL2 were identified as potential upstream regulators driving UM progression.

Conclusions:

• Calibrated AH proteomic profiling can detect clinically relevant protein changes in UM.
• This approach shows potential for developing novel, minimally invasive biomarkers for UM risk stratification and staging.