Aqueous VEGF-A Levels as a Liquid Biopsy Biomarker of Retinoblastoma Vitreous Seed Response to Therapy.
Invest Ophthalmol Vis Sci
; 65(6): 18, 2024 Jun 03.
Article
em En
| MEDLINE
| ID: mdl-38861274
ABSTRACT
Purpose:
Regression of retinoblastoma vitreous seeds (VS) during intravitreal chemotherapy can be delayed, resulting in supernumerary injections. Similarly, VS relapse may not be clinically evident at first. A predictive biomarker of tumor regression and relapse could help guide real-time clinical decision making. Retinoblastoma is an oxygen-sensitive tumor; paradoxically, VS survive in the hypoxic vitreous. We hypothesized that VS elaborate pro-angiogenic cytokines. The purpose was to determine if pro-angiogenic cytokine signatures from aqueous humor could serve as a biomarker of VS response to treatment.Methods:
Multiplex ELISA was performed on aqueous from rabbit eyes with human retinoblastoma VS xenografts to identify expressed proangiogenic cytokines and changes in aqueous cytokine levels during intravitreal treatment were determined. Confirmatory RNAscope in situ hybridization for VEGF-A was performed on human retinoblastoma tumor sections and VS xenografts from rabbits. For human eyes undergoing intravitreal chemotherapy, serial aqueous VEGF-A levels measured via VEGF-A-specific ELISA were compared to clinical response.Results:
VEGF-A was highly expressed in human retinoblastoma VS in the xenograft model, and was the only proangiogenic cytokine that correlated with VS disease burden. In rabbits, aqueous VEGF-A levels decreased in response to therapy, consistent with quantitative VS reduction. In patients, aqueous VEGF-A levels associated with clinical changes in disease burden (regression, stability, or relapse), with changes in VEGF-A levels correlating with clinical response.Conclusions:
Aqueous VEGF-A levels correlate with extent of retinoblastoma VS, suggesting that aqueous VEGF-A may serve as a predictive molecular biomarker of treatment response.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Humor Aquoso
/
Retinoblastoma
/
Corpo Vítreo
/
Ensaio de Imunoadsorção Enzimática
/
Biomarcadores Tumorais
/
Neoplasias da Retina
/
Fator A de Crescimento do Endotélio Vascular
/
Injeções Intravítreas
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
/
Investig. ophthalmol. vis. sci. (Online)
/
Investigative ophthalmology & visual science (Online)
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos