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Research Article: Reduced serum Dickkopf-1 levels as a potential supportive biomarker for the development and severity of retinopathy of prematurity: a prospective observational clinical study

Date Published: 2026-09-28

Abstract:
Retinopathy of prematurity (ROP) involves impaired retinal vascular development, in which the Wnt/?-catenin signaling pathway plays a pivotal role in retinal vasculogenesis and angiogenesis. Dickkopf-1 (DKK-1) is a key endogenous inhibitor of this pathway. This study aimed to evaluate serum DKK-1 levels in preterm infants and explore its potential as a supportive biomarker associated with ROP development and severity. In this prospective observational clinical study, preterm infants with a gestational age ?32 weeks or birth weight ?1500?g were enrolled. Serum DKK-1 levels were measured via ELISA. ROP was classified according to the International Classification of Retinopathy of Prematurity (ICROP). Clinical characteristics and DKK-1 levels were compared between infants with ROP and a control group. Diagnostic performance was evaluated using Receiver Operating Characteristic (ROC) analysis, and independent risk factors were identified via multivariable logistic regression. A total of 60 preterm infants were included, of whom 39 had ROP and 21 served as controls. Serum DKK-1 levels were significantly lower in infants with ROP compared to the control group (median 456.1pg/mL vs. 537.2pg/mL; p =?0.033). A stepwise decline in DKK-1 levels was observed as disease severity increased, with the lowest levels found in the treatment-requiring (TR) ROP subgroup. Although the overall comparison among the three groups did not reach statistical significance (Kruskal–Wallis, p =?0.066), a progressive decline in DKK-1 levels with increasing disease severity was observed. ROC analysis for TR-ROP vs. controls showed an area under the curve (AUC) of 0.679 ( p =?0.041), with 76.2% sensitivity and 75.0% specificity at a cut-off of 480.41pg/mL. Multivariable logistic regression revealed that gestational age was the only independent predictor for ROP ( p =?0.002), while DKK-1 levels showed a biological but not independent association in the model ( p =?0.199). Reduced serum DKK-1 levels were associated with the presence and increasing severity of ROP. Although DKK-1 was not an independent predictor in multivariable analysis, these findings suggest that it may serve as a potential supportive biomarker for identifying infants at increased risk of severe ROP. Further large-scale, multicenter studies are needed to validate its clinical utility and to clarify its role in the Wnt/?-catenin signaling pathway.

Introduction:
Retinopathy of prematurity (ROP) involves impaired retinal vascular development, in which the Wnt/?-catenin signaling pathway plays a pivotal role in retinal vasculogenesis and angiogenesis. Dickkopf-1 (DKK-1) is a key endogenous inhibitor of this pathway. This study aimed to evaluate serum DKK-1 levels in preterm infants and explore its potential as a supportive biomarker associated with ROP development and severity.

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