Li Chunwang, Huang Shuna, Li Qixuan, Zhuo Lingyun, Kang Yaqing, Liu Penghui, Huang Weilin, Ma Ke, Lin Xinru, Zhuang Weiheng, Chen Darong, Wang Huimin, Yan Lingjun, Wang Dengliang, Lin Yuanxiang, Kang Dezhi, Lin Fuxin
Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian, China.
Department of Neurosurgery, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, Fuzhou, 350212, China.
Sci Rep. 2025 Apr 2;15(1):11284. doi: 10.1038/s41598-025-91141-6.
Familial cerebral cavernous malformation (FCCM), especially severe cases, impose a heavy physical and psychological burden on patients and their families. To explore the differences in plasma biomarker levels between patients with FCCM and their healthy first-degree relatives (FDRs) and between FCCM patients with and without severe chronic disease aggressiveness (CDA). In a cross - sectional study, magnetic resonance imaging (MRI) scanning and genetic testing were performed in patients with multiple CCMs and their FDRs. Subsequently, sixty-seven plasma biomarkers were tested using a customised multiplex bead immunoassay kit. Univariate and multivariate unconditional logistic regression analyses were conducted to determine the associations between plasma factors and the risk of developing FCCM and severe CDA. Receiver operating characteristic (ROC) curves were generated for each independent risk factor. As a result, plasma factors of 37 patients with FCCM and 37 FDRs were examined. Low CD31 (P < 0.001) and BDNF levels (P = 0.013) were independent risk factors for FCCM. The best model was achieved by combining the results of CD31 and BDNF (AUC = 0.845, sensitivity 0.838, specificity 0.784, cutoff score - 4.295) to distinguish patients with FCCM from healthy FDRs. Low Serpin E1/PAI-1 (P = 0.011) and high ROBO4 levels (P = 0.013) were independent risk factors for severe CDA in patients with FCCM. The best model was achieved by combining the results of Serpin E1/PAI-1 and ROBO4 levels (AUC = 0.913, sensitivity 1.000, specificity 0.760, cutoff score - 0.525) to identify patients with FCCM and severe CDA. In summary, the plasma concentrations of CD31 and BDNF seem to be lower in patients with FCCM than in their healthy FDRs. Low Serpin E1/PAI-1 and high ROBO4 concentrations may be correlated with high lesion burden and risk of recurrent bleeding.Trial registration: ClinicalTrials.gov Identifier: NCT03467295.
家族性脑海绵状血管畸形（FCCM），尤其是重症病例，给患者及其家庭带来了沉重的身心负担。为了探究FCCM患者与其健康一级亲属（FDRs）之间以及有和没有严重慢性疾病侵袭性（CDA）的FCCM患者之间血浆生物标志物水平的差异。在一项横断面研究中，对患有多发性CCM的患者及其FDRs进行了磁共振成像（MRI）扫描和基因检测。随后，使用定制的多重微珠免疫分析试剂盒检测了67种血浆生物标志物。进行单变量和多变量无条件逻辑回归分析，以确定血浆因子与发生FCCM和严重CDA风险之间的关联。为每个独立危险因素生成了受试者工作特征（ROC）曲线。结果，检测了37例FCCM患者和37例FDRs的血浆因子。低CD31（P < 0.001）和BDNF水平（P = 0.013）是FCCM的独立危险因素。通过结合CD31和BDNF的结果（AUC = 0.845，敏感性0.838，特异性0.784，临界值-4.295）实现了区分FCCM患者与健康FDRs的最佳模型。低丝氨酸蛋白酶抑制剂E1/纤溶酶原激活物抑制剂-1（Serpin E1/PAI-1）（P = 0.011）和高ROBO4水平（P = 0.013）是FCCM患者发生严重CDA的独立危险因素。通过结合Serpin E1/PAI-1和ROBO4水平的结果（AUC = 0.913，敏感性1.000，特异性0.760，临界值-0.525）实现了识别FCCM和严重CDA患者的最佳模型。总之，FCCM患者的血浆CD31和BDNF浓度似乎低于其健康FDRs。低Serpin E1/PAI-1和高ROBO4浓度可能与高病变负荷和复发性出血风险相关。试验注册：ClinicalTrials.gov标识符：NCT03467295。
