{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:57:02Z","timestamp":1790575022356,"version":"4.1.0"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Retinopathy of prematurity (ROP) involves impaired retinal vascular development, in which the Wnt\/\u03b2-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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective observational clinical study, preterm infants with a gestational age \u226432 weeks or birth weight \u22641500\u2005g 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.033). 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\u2013Wallis,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.066), 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 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.041), 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 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002), while DKK-1 levels showed a biological but not independent association in the model (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.199).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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\/\u03b2-catenin signaling pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1917348","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:43:39Z","timestamp":1790574219000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Reduced serum Dickkopf-1 levels as a potential supportive biomarker for the development and severity of retinopathy of prematurity: a prospective observational clinical study"],"prefix":"10.3389","volume":"14","author":[{"given":"Nuriye","family":"Emiro\u011flu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Necmettin Erbakan University","place":["Konya, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan","family":"\u00c7etin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Necmettin Erbakan University","place":["Konya, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00fcseyin","family":"Altunhan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Necmettin Erbakan University","place":["Konya, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnhal","family":"\u015eat\u0131rtav","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, Necmettin Erbakan University","place":["Konya, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saime","family":"Uygun","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Sel\u00e7uk University","place":["Konya, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1871","DOI":"10.1161\/CIRCULATIONAHA.111.040337","article-title":"Wnt signaling mediates pathological vascular growth in proliferative retinopathy","volume":"124","author":"Chen","year":"2011","journal-title":"Circulation"},{"key":"B2","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.preteyeres.2018.11.008","article-title":"Wnt signaling in vascular eye diseases","volume":"70","author":"Wang","year":"2019","journal-title":"Prog Retin Eye Res"},{"key":"B3","doi-asserted-by":"publisher","first-page":"11877","DOI":"10.3390\/ijms222111877","article-title":"Wnt signaling in inner blood-retinal barrier maintenance","volume":"22","author":"Yemanyi","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B4","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41392-021-00762-6","article-title":"Wnt\/\u03b2-catenin signalling: function, biological mechanisms, and therapeutic opportunities","volume":"7","author":"Liu","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"B5","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1038\/eye.2013.229","article-title":"Plasma and vitreous fluid levels of dickkopf-1 in patients with diabetic retinopathy","volume":"28","author":"Qiu","year":"2014","journal-title":"Eye (Lond)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.bbrc.2022.05.001","article-title":"Dickkopf-1 exerts protective effects by inhibiting PANoptosis and retinal neovascularization in diabetic retinopathy","volume":"617","author":"Xu","year":"2022","journal-title":"Biochem Biophys Res Commun"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1038\/s41598-017-01119-2","article-title":"Decreased circulating levels of dickkopf-1 in patients with exudative age-related macular degeneration","volume":"7","author":"Qiu","year":"2017","journal-title":"Sci Rep"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e51","DOI":"10.2353\/ajpath.2009.080945","article-title":"International classification of retinopathy of prematurity, third edition","volume":"128","author":"Chiang","year":"2021","journal-title":"Ophthalmology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1684","DOI":"10.1001\/archopht.121.12.1684","article-title":"Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial","volume":"121","year":"2003","journal-title":"Arch Ophthalmol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"105715","DOI":"10.1016\/j.visres.2017.02.007","article-title":"Guideline development groups (GDG) of the royal college of paediatrics and child health (RCPCH) and the royal college of ophthalmologists (RCOphth). 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