Abstract
Purpose :
GNAQ, BAP1, SF3B1 and EIF1AX mutations have a relevant role in the clinical and prognostic course of posterior uveal melanoma (UM). Detection of aqueous humor (AH) proteins level changes related to these mutations may have novel clinical and prognostic implications in UM eyes. The purpose of this study was to quantify these specific AH protein levels in eyes affected by UM.
Methods :
Seventy-two eyes affected by primary UM were included. Tumor thickness and largest basal diameter were specific clinical characteristics. Tumors were staged with the 8th AJCC classification. During brachytherapy (Iodine-125) surgical procedure, both AH sample collection and 25-gauge transscleral fine needle aspiration biopsy (FNAB) were performed. AH samples were analyzed by immunoprecipitation and SDS PAGE techniques to quantify GNAQ, BAP1, SF3B1 and EIF1AX proteins. Cytologic material underwent fluorescence in situ hybridization for chromosome 3 analysis. The AH of seventy normal eyes was used as control.
Results :
Compared with the control group, significantly higher protein levels of: GNAQ (p=0.02), BAP1 (p=0.01) and SF3B1 (p=0.02) were detected in eyes with UM. Cluster analysis of UM group revealed 2 clusters, one showing higher expression of GNAQ and BAP1 protein and one of EIF1AX protein. These two clusters corresponded with the chromosome 3 status of UM. Moreover, protein analysis revealed the presence of low, medium and high expression levels for each protein, that correlated with UM prognosis (p=0.03).
Conclusions :
UM genetics allows to define in details the pathophysiology and prognosis of this tumor and discoveries on the role of GNAQ, BAP1, EIF1AX and SF3B1 are revolutionizing ocular oncology. Unfortunately, genetic studies often require invasive and/or expensive techniques, whereas proteomic analysis of the AH allows to obtain information on GNAQ, BAP1, EIF1AX and SF3B1 in a relatively simple and precise way. These findings not only confirm the possibilities offered by AH analysis in eyes harboring a UM, but strengthen that AH evaluation may represent the liquid biopsy approach in UM prognosis.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.