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半乳糖凝集素-9:一种预测性生物标志物,可负向调节胶质瘤患者的免疫反应。

Galectin-9: A Predictive Biomarker Negatively Regulating Immune Response in Glioma Patients.

机构信息

Department of Neurosurgery, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Department of Pathology, Capital Medical University, Beijing.

出版信息

World Neurosurg. 2019 Dec;132:e455-e462. doi: 10.1016/j.wneu.2019.08.117. Epub 2019 Aug 27.

Abstract

BACKGROUND

Glioma is the most frequent primary brain tumor. Immunotherapy is one of the most promising therapeutic approaches for gliomas. T cell immunoglobulin domain and mucin domain-3 can induce the malignancy of gliomas. The function of galectin-9 (GAL-9), as one of the ligands of T cell immunoglobulin domain and mucin domain-3, in glioma has remained elusive. The aim of this study was to characterize the expression of GAL-9 in patients with glioma.

METHODS

This study enrolled 1292 patients with glioma from the GSE 16011 array set, the Chinese Glioma Genome Atlas, and The Cancer Genome Atlas datasets. Kaplan-Meier analysis was undertaken to explore the prognostic value of GAL-9. Graphpad software and R language were used for statistical analysis.

RESULTS

Expression of GAL-9 was highly correlated with major clinical and molecular features. Patients with high expression of GAL-9 were more susceptible to development of malignant tumors. Gene Ontology analysis revealed that expression of GAL-9 was closely associated with function of immune response in glioma. Clinically, the results of Kaplan-Meier analysis showed that expression of GAL-9 was negatively associated with overall survival in all grades of glioma including high-grade gliomas. High expression of GAL-9 was an independent indicator of poor prognosis.

CONCLUSIONS

Our results highlight the pivotal role of GAL-9 in regulation of immune suppressive features of gliomas and indicate that GAL-9 is a promising target for cancer immunotherapy and may lead to development of further therapies.

摘要

背景

脑胶质瘤是最常见的原发性脑肿瘤。免疫疗法是脑胶质瘤最有前途的治疗方法之一。T 细胞免疫球蛋白结构域和粘蛋白结构域-3 可诱导脑胶质瘤的恶性转化。半乳糖凝集素-9(GAL-9)作为 T 细胞免疫球蛋白结构域和粘蛋白结构域-3 的配体之一,在脑胶质瘤中的功能仍不清楚。本研究旨在研究 GAL-9 在脑胶质瘤患者中的表达特征。

方法

本研究纳入了来自 GSE16011 数组集、中国脑胶质瘤基因组图谱和癌症基因组图谱数据库的 1292 例脑胶质瘤患者。采用 Kaplan-Meier 分析探讨 GAL-9 的预后价值。Graphpad 软件和 R 语言用于统计分析。

结果

GAL-9 的表达与主要的临床和分子特征高度相关。GAL-9 高表达的患者更容易发生恶性肿瘤。基因本体论分析显示,GAL-9 的表达与脑胶质瘤的免疫反应功能密切相关。临床上,Kaplan-Meier 分析结果表明,GAL-9 的表达与所有级别包括高级别脑胶质瘤患者的总生存期呈负相关。GAL-9 的高表达是预后不良的独立指标。

结论

我们的研究结果强调了 GAL-9 在调节脑胶质瘤免疫抑制特征中的关键作用,并表明 GAL-9 是癌症免疫治疗的有前途的靶点,并可能导致进一步治疗方法的发展。

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