Angiopoietins as serum biomarkers for lymphatic anomalies

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• 作者：Timothy D. Le Cras ; Paula S. Mobberley-Schuman ; Mary Broering ; Lin Fei…
• 关键词：Vascular anomalies ; Generalized lymphatic anomaly ; Kaposiform lymphangiomatosis ; Kaposiform hemangioendothelioma ; Sirolimus ; Kasabach–Merritt
• 刊名：Angiogenesis
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：20
• 期：1
• 页码：163-173
• 全文大小：
• 刊物类别：Medicine
• 刊物主题：Cancer Research; Biomedicine, general; Cell Biology; Cardiology; Ophthalmology; Oncology;
• 出版者：Springer Netherlands
• ISSN：1573-7209
• 卷排序：20

文摘

Vascular anomalies can cause significant morbidity and mortality. Advances in diagnosis will be improved if noninvasive biomarkers can be identified, as obtaining a tissue biopsy can worsen the disease and precipitate complications. The goal of this study was to identify biomarkers for vascular anomaly patients to aid diagnosis and potentially give insights into pathogenesis. Blood was collected at baseline and then 6 and 12 months after treatment with the mTOR inhibitor sirolimus. Patients groups included generalized lymphatic anomaly (GLA), kaposiform lymphangiomatosis (KLA) and kaposiform hemangioendothelioma (KHE) with or without the Kasabach–Merritt phenomenon (KMP) coagulopathy. Serum was obtained from healthy controls selected to match the age and sex of the patients (21 days–28.5 years; 42% males; 58% females). Angiogenic and lymphangiogenic factors (VEGF-A, C, D, Ang-1 and Ang-2) were measured in serum using ELISA. In lymphatic anomaly patients, baseline levels of VEGF-A and VEGF-D were not different compared to controls. Angiopoietin-2 (Ang-2) levels were near controls levels in GLA patients but 10-fold greater in KLA patients and 14-fold greater in KHE patients when the KMP coagulopathy was present but not when it was absent. VEGF-C and angiopoietin-1 (Ang-1) levels were lower in KHE patients with KMP. Our analyses suggest that Ang-2 and Ang-1 can be used as biomarkers to help identify KLA and KHE patients with KMP coagulopathy with high sensitivity and specificity. After 12 months of sirolimus treatment, Ang-2 levels were lower in KLA and KHE with KMP patients compared to baseline levels and with most patients showing a clinical response. Hence, serum Ang-2 and Ang-1 levels may help in the diagnosis of patients with lymphatic anomalies and are concordant to sirolimus response.