Cakmak Hatice Mine, Kiliccioglu Ilker, Dulger Gorkem
Department of Pediatrics, Pediatric Hematology-Oncology, Duzce University School of Medicine, Duzce, Turkey.
Department of Medical Biology, Duzce University School of Medicine, Duzce, Turkey.
Eur J Pediatr. 2025 Jul 11;184(8):476. doi: 10.1007/s00431-025-06311-5.
Infantile hemangioma (IH) is the most common vascular tumor in infancy. This study aimed to investigate serum levels of VEGF-B, AKT, and eNOS in complicated versus uncomplicated cases of infantile hemangioma and evaluate their correlation with clinical regression scores over time. In this prospective study, we followed 64 patients with intrahospital hemorrhage (IH). Patients were grouped into two categories: complicated (n = 44) and uncomplicated (n = 20). Serum/plasma samples were collected on day 0 from all patients and on days 30 and 60 from complicated cases. ELISA techniques were used to quantify serum VEGF-B, AKT, and eNOS levels. A novel four-domain clinical regression scoring system (size, color, surface, and vascular activity; total 0-12 points) was developed and applied for the first 3 months of follow-up at each visit. VEGF-B, AKT, and eNOS serum levels were significantly higher at baseline in complicated IH and decreased over time with regression. However, AKT serum levels showed a significant decline only in the days of 60 (p = 0.043). Clinical regression scores increased in parallel, with substantial differences between healed and non-healed cases. ROC analysis revealed that day 30 and day 60 clinical scores strongly predicted complete healing (AUC = 0.739 and 0.850, respectively).
The VEGF-B/VEGFR-1, AKT/mTOR, and eNOS pathways appear central to IH pathogenesis. Serum levels of these molecules may serve as dynamic biomarkers of disease phase and response to therapy. This study contributes novel data supporting potential targets for future personalized treatment strategies with a novel 3-month follow-up regression score predicting resolution.
• Angiogenic mediators such as VEGF-A, bFGF, Akt, and eNOS are elevated during the proliferative phase of infantile hemangioma and decline with propranolol treatment. • Previous studies have primarily investigated tissue-level expression, and there is limited clinical data on serum VEGF-B, Akt, and eNOS levels in IH patients.
• This is the first clinical study to longitudinally measure serum VEGF-B, AKT, and eNOS levels in infantile hemangioma patients and track their changes during treatment-induced involution. • A novel, four-domain clinical regression scoring system (size, color, surface, vascular activity) was introduced and shown to predict treatment response within the first 60 days of follow-up.
婴儿血管瘤（IH）是婴儿期最常见的血管肿瘤。本研究旨在调查复杂型与非复杂型婴儿血管瘤病例中血管内皮生长因子B（VEGF - B）、蛋白激酶B（AKT）和内皮型一氧化氮合酶（eNOS）的血清水平，并评估它们与临床消退评分随时间的相关性。在这项前瞻性研究中，我们对64例患有医院内出血的婴儿血管瘤患者进行了随访。患者分为两类：复杂型（n = 44）和非复杂型（n = 20）。在第0天采集所有患者的血清/血浆样本，在第30天和第60天采集复杂型病例的样本。采用酶联免疫吸附测定（ELISA）技术定量血清VEGF - B、AKT和eNOS水平。开发了一种新的四维度临床消退评分系统（大小、颜色、表面和血管活性；总分0 - 12分），并在每次随访的前3个月应用。复杂型婴儿血管瘤患者基线时VEGF - B、AKT和eNOS血清水平显著更高，并随消退而随时间下降。然而，AKT血清水平仅在第60天出现显著下降（p = 0.043）。临床消退评分平行增加，愈合和未愈合病例之间存在显著差异。ROC分析显示，第30天和第60天的临床评分强烈预测完全愈合（AUC分别为0.739和0.850）。
VEGF - B/VEGFR - 1、AKT/mTOR和eNOS通路似乎在婴儿血管瘤发病机制中起核心作用。这些分子的血清水平可能作为疾病阶段和治疗反应的动态生物标志物。本研究提供了新的数据，支持未来个性化治疗策略的潜在靶点，一种新的3个月随访消退评分可预测消退情况。
•血管生成介质如血管内皮生长因子A（VEGF - A）、碱性成纤维细胞生长因子（bFGF）、Akt和eNOS在婴儿血管瘤增殖期升高，并随普萘洛尔治疗而下降。•以往研究主要调查组织水平的表达，关于婴儿血管瘤患者血清VEGF - B、Akt和eNOS水平的临床数据有限。
•这是第一项纵向测量婴儿血管瘤患者血清VEGF - B、AKT和eNOS水平并跟踪其在治疗诱导消退过程中变化的临床研究。•引入了一种新的四维度临床消退评分系统（大小、颜色、表面、血管活性），并显示可在随访的前60天内预测治疗反应。
