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).Conclusion: 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.<Table Float="No" ID="Taba"> <tgroup cols="1"> <colspec align="left" colname="c1" colnum="1" /> <tbody> <row> <entry align="left" colname="c1"> What is Known: </entry> </row> <row> <entry align="left" colname="c1"> • Angiogenic mediators such as VEGF-A, bFGF, Akt, and eNOS are elevated during the proliferative phase of infantile hemangioma and decline with propranolol treatment. </entry> </row> <row> <entry align="left" colname="c1"> • 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. </entry> </row> <row> <entry align="left" colname="c1"> What is New: </entry> </row> <row> <entry align="left" colname="c1"> • 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. </entry> </row> <row> <entry align="left" colname="c1"> • 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. </entry> </row> </tbody> </tgroup> </Table>

Dynamic serum biomarkers in infantile hemangioma: the role of VEGF-B, AKT, and eNOS in lesion regression

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发表日期：

2025年7月11日

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Hatice Mine Cakmak,
Ilker Kiliccioglu,
Gorkem Dulger

摘要

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).

Conclusion: 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.

What is Known:

• 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.

What is New:

• 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.