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ITGB2 表达与脑胶质瘤临床特征的相关性及其在低级别胶质瘤(LGG)中甲基化的预后意义。

Correlation between ITGB2 expression and clinical characterization of glioma and the prognostic significance of its methylation in low-grade glioma(LGG).

机构信息

Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.

出版信息

Front Endocrinol (Lausanne). 2023 Jan 13;13:1106120. doi: 10.3389/fendo.2022.1106120. eCollection 2022.

Abstract

INTRODUCTION

Glioma is the most common primary tumor in the brain.Integrin beta 2(ITGB2) is a member of the leukocyte integrin family (leukocyte integrin), participating in lymphocyte recycling and homing, cell adhesion, and cell surface-mediated signal transduction. However, few studies on ITGB2 in gliomas have been reported yet.This study first discussed the relationship between ITGB2 expression and clinical characterization of glioma and the prognostic significance of its methylation in low-grade glioma.

METHODS

We collected Clinical data and transcription of glioma patients from TCGA, CGGA, and Rembrant datasets to analyze the differential expression of ITGB2 mRNA in glioma tissues and normal tissues. The box polts to evaluated the expression patterns of ITGB2 in different molecular subtypes. Receiver operating characteristic curve (ROC) were used to evaluate and verify the reliability of the model. Kaplan-Meier survival curves to evaluated the relationship between the level of ITGB2 mRNA expression and overall survival (OS). Using cox regression analysis to verify the ability of ITGB2 as an independent predictor of OS in glioma patients. We use TIMER to analyze and visualize the association between immune infiltration levels and a range of variables. The methylation of GBMLGG patients were obtained from the TCGA database through the biological portal.

RESULTS

ITGB2 can be a potential marker for mesenchymal molecular subtype gliomas. COX regression analysis shows that ITGB2 is an independent predictive marker of OS in malignant glioma patients. Biological processes show that ITGB2 has involved glioma immune-related activities, especially closely related to B cells, CD4+Tcells, macrophages, neutrophils, and dendritic cells. ITGB2 is negatively regulated by ITGB2 methylation, resulting in low expression in LGG tissues. Low expression of ITGB2 and high methylation indicate good OS in patients with LGG. The ITGB2 methylation risk score (ITMRS) obtained from the ITGB2 methylation CpG site can better predict the OS of LGG patients. We used univariate and multivariate cox regression analysis of methylationsites, used the R language predict function to obtain the risk score of these ITGB2 methylation sites(ITMRS).

DISCUSSION

ITGB2 can be used as a potential marker of mesenchymal molecular subtypes of gliomas and as an independent predictive marker of OS in patients with malignant gliomas. The ITMRS we established can be used as an independent prognostic factor for LGG and provide a new idea for the diagnosis and treatment of LGG.

摘要

简介

脑胶质瘤是最常见的原发性脑肿瘤。整合素β 2(ITGB2)是白细胞整合素家族的成员(白细胞整合素),参与淋巴细胞的再循环和归巢、细胞黏附以及细胞表面介导的信号转导。然而,目前关于脑胶质瘤中 ITGB2 的研究较少。本研究首次探讨了 ITGB2 表达与脑胶质瘤临床特征的关系及其在低级别脑胶质瘤中甲基化的预后意义。

方法

我们从 TCGA、CGGA 和 Rembrant 数据集收集脑胶质瘤患者的临床数据和转录组,以分析 ITGB2 mRNA 在脑胶质瘤组织和正常组织中的差异表达。箱线图评估 ITGB2 在不同分子亚型中的表达模式。接收者操作特征曲线(ROC)用于评估和验证模型的可靠性。Kaplan-Meier 生存曲线评估 ITGB2mRNA 表达水平与总生存期(OS)的关系。使用 COX 回归分析验证 ITGB2 作为脑胶质瘤患者 OS 的独立预测因子的能力。我们使用 TIMER 分析和可视化免疫浸润水平与一系列变量之间的关联。通过生物门户网站从 TCGA 数据库中获取 GBMLGG 患者的甲基化数据。

结果

ITGB2 可以作为间充质分子亚型脑肿瘤的潜在标志物。COX 回归分析表明,ITGB2 是恶性脑胶质瘤患者 OS 的独立预测标志物。生物过程显示,ITGB2 参与了脑胶质瘤的免疫相关活动,特别是与 B 细胞、CD4+T 细胞、巨噬细胞、中性粒细胞和树突状细胞密切相关。ITGB2 受 ITGB2 甲基化的负调控,导致 LGG 组织中表达水平降低。ITGB2 低表达和高甲基化提示 LGG 患者 OS 良好。从 ITGB2 甲基化 CpG 位点获得的 ITGB2 甲基化风险评分(ITMRS)可以更好地预测 LGG 患者的 OS。我们使用单因素和多因素 COX 回归分析甲基化位点,使用 R 语言预测函数获得这些 ITGB2 甲基化位点的风险评分(ITMRS)。

讨论

ITGB2 可作为脑胶质瘤间充质分子亚型的潜在标志物,作为恶性脑胶质瘤患者 OS 的独立预测标志物。我们建立的 ITMRS 可作为 LGG 的独立预后因素,并为 LGG 的诊断和治疗提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f789/9880157/a8ade09c2bbe/fendo-13-1106120-g001.jpg

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