SIGLEC7 的高表达可能促进 M2 型巨噬细胞极化，从而导致胶质瘤患者预后不良。

High expression of SIGLEC7 may promote M2-type macrophage polarization leading to adverse prognosis in glioma patients.

机构信息

Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China.

Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

出版信息

Front Immunol. 2024 Aug 15;15:1411072. doi: 10.3389/fimmu.2024.1411072. eCollection 2024.

DOI:10.3389/fimmu.2024.1411072

PMID:39211050

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11357930/

Abstract

INTRODUCTION

Gliomas are the most common primary intracranial tumors, known for their high invasiveness and destructiveness. Sialic acid-binding immunoglobulin-like lectin 7 (SIGLEC7) is present in various immune cells, especially macrophages, and significantly affects immune homeostasis and cancer cell response. However, research on the role and prognostic impact of SIGLEC7 in glioma patients is currently limited.

METHODS

We utilized transcriptomic data from 702 glioma patients in The Cancer Genome Atlas (TCGA) and 693 glioma patients in the Chinese Glioma Genome Atlas (CGGA), along with clinical samples we collected, to comprehensively investigate the impact of SIGLEC7 on glioma expression patterns, biological functions, and prognostic value. We focused on its role in glioma-related immune responses and immune cell infiltration and analyzed its expression at the single-cell level. Finally, we validated the role of SIGLEC7 in gliomas through tissue and cell experiments.

RESULTS

SIGLEC7 expression was significantly increased in glioma patients with malignant characteristics. Survival analysis indicated that glioma patients with high SIGLEC7 expression had significantly lower survival rates. Gene function analysis revealed that SIGLEC7 is primarily involved in immune and inflammatory responses and is strongly negatively correlated with tumor-associated immune regulation. Additionally, the expression of most immune checkpoints was positively correlated with SIGLEC7, and immune cell infiltration analysis clearly demonstrated a significant positive correlation between SIGLEC7 expression and M2 macrophage infiltration levels. Single-cell analysis, along with tissue and cell experiments, confirmed that SIGLEC7 enhances macrophage polarization towards the M2 phenotype, thereby promoting glioma invasiveness through the immunosuppressive effects of M2 macrophages. Cox regression analysis and the establishment of survival prediction models indicated that high SIGLEC7 expression is an unfavorable prognostic factor for glioma patients.

DISCUSSION

High SIGLEC7 expression predicts poor prognosis in glioma patients and is closely associated with M2 macrophages in the tumor environment. In the future, SIGLEC7 may become a promising target for glioma immunotherapy.

摘要

简介

神经胶质瘤是最常见的原发性颅内肿瘤，以高度侵袭性和破坏性为特征。唾液酸结合免疫球蛋白样凝集素 7（SIGLEC7）存在于各种免疫细胞中，尤其是巨噬细胞中，对免疫稳态和癌细胞反应有显著影响。然而，目前关于 SIGLEC7 在神经胶质瘤患者中的作用和预后影响的研究还很有限。

方法

我们利用了来自癌症基因组图谱（TCGA）的 702 名神经胶质瘤患者和中国神经胶质瘤基因组图谱（CGGA）的 693 名神经胶质瘤患者的转录组数据，以及我们收集的临床样本，全面研究了 SIGLEC7 对神经胶质瘤表达模式、生物学功能和预后价值的影响。我们重点研究了它在神经胶质瘤相关免疫反应和免疫细胞浸润中的作用，并在单细胞水平上分析了其表达。最后，我们通过组织和细胞实验验证了 SIGLEC7 在神经胶质瘤中的作用。

结果

SIGLEC7 在具有恶性特征的神经胶质瘤患者中表达显著增加。生存分析表明，SIGLEC7 高表达的神经胶质瘤患者的生存率显著降低。基因功能分析表明，SIGLEC7 主要参与免疫和炎症反应，与肿瘤相关的免疫调节呈强烈负相关。此外，大多数免疫检查点的表达与 SIGLEC7 呈正相关，免疫细胞浸润分析清楚地表明，SIGLEC7 表达与 M2 巨噬细胞浸润水平呈显著正相关。单细胞分析以及组织和细胞实验均证实，SIGLEC7 增强了巨噬细胞向 M2 表型的极化，从而通过 M2 巨噬细胞的免疫抑制作用促进神经胶质瘤的侵袭。Cox 回归分析和生存预测模型的建立表明，SIGLEC7 高表达是神经胶质瘤患者不良预后的一个不利因素。