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胶质瘤患者中基因多态性和α-klotho蛋白血清水平与不同肿瘤分级、总生存期及细胞因子谱的相关性

Association of Gene Polymorphism and Serum Level of α Klotho Protein with Different Tumor Grades, Overall Survival and Cytokine Profile in Glioma Patients.

作者信息

Zsemlye Eszter, Durmanova Vladimira, Kluckova Kristina, Kozak Jan, Rychly Boris, Svajdler Marian, Matejcik Viktor, Homolova Monika, Steno Juraj, Hunakova Luba, Bucova Maria

机构信息

Institute of Immunology, Faculty of Medicine, Comenius University Bratislava, 813 72 Bratislava, Slovakia.

Clinic for Children and Adolescents, Faculty Hospital Nitra, 950 01 Nitra, Slovakia.

出版信息

Int J Mol Sci. 2025 Jan 2;26(1):330. doi: 10.3390/ijms26010330.

Abstract

Gliomas are the most common and lethal forms of malignant brain tumors. We attempted to identify the role of the aging-suppressor gene and Klotho protein in the immunopathogenesis of gliomas. We examined genetic variants by PCR-RFLP and measured serum Klotho levels using the ELISA method. We found a statistically significantly increased frequency of rs1207568A allele and rs1207568 GA genotypes in co-dominant, dominant and over-dominant models in grade IV as compared to grade II and III glioma patients. The levels of soluble α Klotho (sαKL) were significantly lower in grade III and IV glioma patients than in healthy controls ( = 0.034; 0.0083). Patients with sαKL levels above 2500 pg/mL survived significantly longer than patients with sαKL below 2500 pg/mL ( = 0.038). We also found a positive correlation of the serum levels of sαKL with seven biomarkers, like angiogenic vascular endothelial growth factor ( = 0.0008), chemokine fractalkine ( = 0.0009), interferon γ ( = 0.003), glial derived neurotrophic factor ( = 0.0268), pro-inflammatory and pro-Th1 cytokine IL-6 ( = 0.0347), anti-inflammatory, pro-Th2 cytokines IL-4 ( = 0.0037) and IL-13 ( = 0.0004). Our results suggest the impact of genetic variants and Klotho levels on advanced-grade glioma.

摘要

神经胶质瘤是最常见且致命的恶性脑肿瘤形式。我们试图确定衰老抑制基因和α-klotho蛋白在神经胶质瘤免疫发病机制中的作用。我们通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测基因变异,并使用酶联免疫吸附测定(ELISA)方法测量血清α-klotho水平。我们发现,与II级和III级神经胶质瘤患者相比,IV级神经胶质瘤患者在共显性、显性和超显性模型中,rs1207568A等位基因和rs1207568 GA基因型的频率在统计学上显著增加。III级和IV级神经胶质瘤患者的可溶性α-klotho(sαKL)水平显著低于健康对照组(P = 0.034;0.0083)。sαKL水平高于2500 pg/mL的患者比sαKL水平低于2500 pg/mL的患者存活时间显著更长(P = 0.038)。我们还发现sαKL血清水平与七种生物标志物呈正相关,如血管生成性血管内皮生长因子(P = 0.0008)、趋化因子fractalkine(P = 0.0009)、干扰素γ(P = 0.003)、胶质细胞源性神经营养因子(P = 0.0268)、促炎和促Th1细胞因子白细胞介素-6(IL-6,P = 0.0347)、抗炎、促Th2细胞因子白细胞介素-4(IL-4,P = 0.0037)和白细胞介素-13(IL-13,P = 0.0004)。我们的结果表明基因变异和α-klotho水平对高级别神经胶质瘤有影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5ac/11719750/c806abb5783c/ijms-26-00330-g001.jpg

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