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HLA-G 14bp插入/缺失多态性、可溶性HLA-G血浆水平及其与胶质瘤患者白细胞介素-6/白细胞介素-10比值和生存的关联

HLA-G 14bp Ins/Del Polymorphism, Plasma Level of Soluble HLA-G, and Association with IL-6/IL-10 Ratio and Survival of Glioma Patients.

作者信息

Bucova Maria, Kluckova Kristina, Kozak Jan, Rychly Boris, Suchankova Magda, Svajdler Marian, Matejcik Viktor, Steno Juraj, Zsemlye Eszter, Durmanova Vladimira

机构信息

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

Department of Neurosurgery, Faculty of Medicine, Comenius University and University Hospital, 833 05 Bratislava, Slovakia.

出版信息

Diagnostics (Basel). 2022 Apr 27;12(5):1099. doi: 10.3390/diagnostics12051099.

Abstract

HLA-G is an immune checkpoint molecule with immunosuppressive and anti-inflammatory activities, and its expression and level of its soluble form (sHLA-G) may play an important role in tumor prognosis. The HLA-G 14bp ins/del polymorphism and the plasma level of soluble HLA-G (sHLA-G) were investigated by a polymerase chain reaction and ELISA, respectively, in 59 glioma patients. A significantly higher proportion of glioma patients had the 14 nt insert in both homozygous and heterozygous states compared to the control group. Glioma patients also had higher plasma levels of sHLA-G. Patients with methylated MGMT promoters had lower levels of sHLA-G than those with unmethylated MGMT promoters. The level of sHLA-G negatively correlated with the overall survival of patients. Glioblastoma patients who survived more than one year after diagnosis had lower levels of sHLA-G than those surviving less than one year. Patients with sHLA-G levels below the cut-off value of 40 U/mL survived significantly longer than patients with sHLA-G levels above 40 U/mL. The levels of sHLA-G were also negatively correlated with the level of IL-6 ( = 0.0004) and positively with IL-10/IL-6 ( = 0.046). Conclusion: The presence of the 14 nt insert in both homozygous and heterozygous states of the HLA-G 14bp ins/del polymorphism is more frequent in glioma patients and the elevated plasma levels of sHLA-G are negatively associated with their survival.

摘要

HLA - G是一种具有免疫抑制和抗炎活性的免疫检查点分子,其表达及其可溶性形式(sHLA - G)的水平可能在肿瘤预后中起重要作用。分别采用聚合酶链反应和酶联免疫吸附测定法,对59例神经胶质瘤患者的HLA - G 14bp插入/缺失多态性和可溶性HLA - G(sHLA - G)血浆水平进行了研究。与对照组相比,神经胶质瘤患者中纯合子和杂合子状态下14个核苷酸插入的比例显著更高。神经胶质瘤患者的sHLA - G血浆水平也更高。甲基化MGMT启动子的患者sHLA - G水平低于未甲基化MGMT启动子的患者。sHLA - G水平与患者的总生存期呈负相关。诊断后存活超过一年的胶质母细胞瘤患者的sHLA - G水平低于存活少于一年的患者。sHLA - G水平低于临界值40 U/mL的患者的生存期明显长于sHLA - G水平高于40 U/mL的患者。sHLA - G水平也与IL - 6水平呈负相关( = 0.0004),与IL - 10/IL - 6呈正相关( = 0.046)。结论:HLA - G 14bp插入/缺失多态性的纯合子和杂合子状态下14个核苷酸插入在神经胶质瘤患者中更常见,sHLA - G血浆水平升高与其生存期呈负相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8c8/9139224/51f533fd70e5/diagnostics-12-01099-g001.jpg

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