Glioblastoma, the deadliest adult brain tumor, poses a significant therapeutic challenge with a dismal prognosis despite current treatments. Zonulin, a protein influencing tight junctions and barrier functions, has gained attention for its diverse roles in various diseases. This study aimed to preliminarily analyze the circulating and tumor zonulin levels, evaluating their impact on disease prognosis and clinical–radiological factors. Additionally, we investigated in vitro zonulin expression in different glioblastoma cell lines under two different conditions. The study comprised 34 newly diagnosed glioblastoma patients, with blood samples collected before treatment for zonulin and haptoglobin analysis. Tumor tissue samples from 21 patients were obtained for zonulin expression. Clinical, molecular, and radiological data were collected, and zonulin protein levels were assessed using ELISA and Western blot techniques. Furthermore, zonulin expression was analyzed in vitro in three glioblastoma cell lines cultured under standard and glioma-stem-cell (GSC)-specific conditions. High zonulin expression in glioblastoma tumors correlated with larger preoperative contrast enhancement and edema volumes. Patients with high zonulin levels showed a poorer prognosis (progression-free survival [PFS]). Similarly, elevated serum levels of zonulin were associated with a trend of shorter PFS. Higher haptoglobin levels correlated with MGMT methylation and longer PFS. In vitro, glioblastoma cell lines expressed zonulin under standard cell culture conditions, with increased expression in tumorsphere-specific conditions. Elevated zonulin levels in both the tumor and serum of glioblastoma patients were linked to a poorer prognosis and radiological signs of increased disruption of the blood–brain barrier. In vitro, zonulin expression exhibited a significant increase in tumorspheres.
胶质母细胞瘤作为成人中最致命的脑肿瘤，尽管现有治疗手段不断进步，其预后依然极差，构成了重大的治疗挑战。连蛋白作为一种影响紧密连接和屏障功能的蛋白质，因其在多种疾病中的广泛作用而受到关注。本研究旨在初步分析循环系统及肿瘤组织中的连蛋白水平，评估其对疾病预后及临床-放射学因素的影响。同时，我们在两种不同条件下研究了不同胶质母细胞瘤细胞系中连蛋白的体外表达情况。研究纳入了34例新诊断的胶质母细胞瘤患者，在治疗前采集血液样本用于连蛋白和结合珠蛋白分析，并从其中21例患者获取肿瘤组织样本进行连蛋白表达检测。通过ELISA和Western blot技术评估连蛋白水平，并收集临床、分子及放射学数据。此外，在标准培养条件和胶质瘤干细胞特异性培养条件下，对三种胶质母细胞瘤细胞系进行了连蛋白表达的体外分析。研究发现，胶质母细胞瘤组织中高表达的连蛋白与术前更大的对比增强体积和水肿体积相关。连蛋白高水平患者的预后更差（无进展生存期缩短）。同样，血清连蛋白水平升高也呈现出无进展生存期缩短的趋势。而较高的结合珠蛋白水平则与MGMT基因甲基化及更长的无进展生存期相关。体外实验显示，胶质母细胞瘤细胞系在标准培养条件下表达连蛋白，且在肿瘤球特异性培养条件下表达显著增加。胶质母细胞瘤患者肿瘤组织和血清中连蛋白水平升高与不良预后及血脑屏障破坏加剧的放射学征象相关。体外实验中，连蛋白在肿瘤球形成条件下表达显著增强。
Evaluation of Zonulin Expression and Its Potential Clinical Significance in Glioblastoma
肿瘤(癌症)患者之家