Abstract 3667: Nucleic acid quantification in uveal melanoma aqueous humor

Abstract Introduction: Uveal melanoma (UM) is the most common primary adult intraocular cancer. Though radiation brachytherapy is often employed for UM treatment, half of UM patients develop systemic metastases. In large tumors with macular involvement, the disease and its treatment can lead to blindness. Clinically, UM prognosis is estimated by tumor size, location, American Joint Cancer Commission (AJCC) staging, and histologic findings. Prognostic UM biomarkers have been established but lesions <2 mm in height, particularly near the fovea, are difficult to biopsy, and thus physicians often do not perform biopsies on such tumors. Therefore, the use of aqueous humor (AH) as a liquid biopsy is a promising methodology. The purpose of the study was to quantify analytes in AH samples collected at diagnosis and post-brachytherapy from UM eyes with varying tumor sizes and AJCC Stages to analyze correlations between analyte (dsDNA, microDNA, and protein) concentrations and tumor features. Methods: This case series study included 119 UM AH samples from 66 UM eyes and 16 control AH samples collected from age-matched non-UM glaucoma (GLC) eyes analyzed for unprocessed analytes using Qubit fluorescence assays. Results: Most UM AH samples contained quantifiable analyte concentrations (dsDNA: 94.1%, miRNA: 88.0%, protein: 95.2%) and at higher concentrations than GLC controls (dsDNA, P=0.008; miRNA, P<0.0001; protein, P=0.007). In samples taken at diagnosis, concentrations were higher at more advanced AJCC stages; comparing most advanced Stage III (n=8) to least advanced Stage I (n=24), median dsDNA was 4 times greater (P<0.0001), protein was 3 times greater (P<0.0001), and miRNA was 2 times greater (P=0.001). Analytes were quantifiable in >70% of pre-brachytherapy samples from eyes with tumors <2 mm tall (n=17). Height was positively associated with analyte concentrations at diagnosis (dsDNA: R=0.43, P=0.0007; miRNA: R=0.35, P=0.01; protein: R=0.39, P=0.005). In paired samples (n=53), all analyte concentrations were significantly higher post-therapy compared to diagnosis pre-therapy (Ps<0.01). Conclusions: Although AH analytes were also quantifiable in smaller, less advanced tumors, AH samples from eyes with larger, more advanced tumors had higher analyte concentrations. The detection of prognostic biomarkers in AH may allow for early UM recognition and guide personalized treatment. Citation Format: Christina Chang, Sarah Pike, Mark Reid, Chen-Ching Peng, Benjamin Xu, Jesse Berry, Liya Xu. Nucleic acid quantification in uveal melanoma aqueous humor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3667.