Jaimes-Díaz Sherlyne, Juan-Samper Gustavo, Torres-Martínez Susana, Escorihuela-Alares Eva, Calabuig-Fariñas Silvia, Rodríguez-López Raquel, Prieto-Colodrero Nieves, Ramon-Capilla Mercedes, Fernández-Fabrellas Estrella
Pneumology Department, General University Hospital of Valencia, 46014 Valencia, Spain.
Molecular Oncology Laboratory, General University Hospital of Valencia, 46014 Valencia, Spain.
Diagnostics (Basel). 2024 Dec 11;14(24):2783. doi: 10.3390/diagnostics14242783.
: Angiogenesis is involved in the pathogenesis of hereditary hemorrhagic telangiectasia (HHT). VEGF, ANG2, TGFβ1, and ENG are the most studied angiogenic factors, but their clinical significance in blood samples is still not completely defined. The genetic study of HHT mutations is the test of choice for diagnosing the disease, but this route is expensive, and the causative mutation is not found in up to 10% of cases. Therefore, the use of angiogenic biomarkers could facilitate a cheaper and easier approach to the diagnosis of HHT. To determine the diagnostic and prognostic value of the VEGFA, TGFβ1, ANG2, and ENG plasmatic concentrations in patients with HHT. : All the participants were clinically evaluated and the concentrations of these angiogenic factors were measured using MILLIPLEXMAP immunoassays in plasma samples collected from 44 patients with HHT and 19 controls. To evaluate the diagnostic validity of these parameters, we estimated the maximum Youden index of the ROC curve and evaluated their diagnostic value using multiple logistic regression. : Patients with HHT had increased blood levels of TGFβ1 and decreased ENG compared to the control group. We could not identify any angiogenic markers related to the clinical severity or epistaxis. TGFβ1 and ENG exhibited a higher discriminant capacity for HHT, especially patients with HHT1, and it was possible to develop signatures of these factors with diagnostic value. : We identified several angiogenic factors that may be important diagnostic biomarkers for HHT and propose that the combination of TGFβ1 and ENG could represent a signature with diagnostic value for this disease.
血管生成参与遗传性出血性毛细血管扩张症（HHT）的发病机制。血管内皮生长因子（VEGF）、血管生成素2（ANG2）、转化生长因子β1（TGFβ1）和内皮糖蛋白（ENG）是研究最多的血管生成因子，但其在血液样本中的临床意义仍未完全明确。HHT突变的基因研究是诊断该病的首选检测方法，但该方法费用高昂，且高达10%的病例未发现致病突变。因此，使用血管生成生物标志物有助于以更便宜、更简便的方法诊断HHT。确定VEGFA、TGFβ1、ANG2和ENG血浆浓度在HHT患者中的诊断和预后价值。：对所有参与者进行临床评估，并使用MILLIPLEXMAP免疫测定法测量从44例HHT患者和19名对照者采集的血浆样本中这些血管生成因子的浓度。为评估这些参数的诊断有效性，我们估计了ROC曲线的最大约登指数，并使用多元逻辑回归评估其诊断价值。：与对照组相比，HHT患者的TGFβ1血液水平升高，ENG降低。我们未发现任何与临床严重程度或鼻出血相关的血管生成标志物。TGFβ1和ENG对HHT，尤其是HHT1患者表现出更高的判别能力，并且有可能开发出具有诊断价值的这些因子的特征。：我们鉴定了几种可能是HHT重要诊断生物标志物的血管生成因子，并提出TGFβ1和ENG的组合可能代表该疾病具有诊断价值的特征。
