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SIGLEC7的高表达可能促进M2型巨噬细胞极化,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.

发表日期:2024
作者: Wenhao An, Changyuan Ren, Lei Yuan, Zhiqiang Qiu, Peishen Wang, Yanwen Cheng, Zi He, Xinye Han, Shouwei Li, Yihua An
来源: Frontiers in Immunology

摘要:

神经胶质瘤是最常见的原发性颅内肿瘤,以其高侵袭性和破坏性而闻名。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,并显着影响免疫稳态和癌细胞反应。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有限。我们利用了癌症基因组图谱 (TCGA) 中 702 名神经胶质瘤患者和中国神经胶质瘤基因组图谱 (CGGA) 中 693 名神经胶质瘤患者的转录组数据,以及我们收集了临床样本,全面研究 SIGLEC7 对胶质瘤表达模式、生物学功能和预后价值的影响。我们重点关注其在神经胶质瘤相关免疫反应和免疫细胞浸润中的作用,并在单细胞水平分析其表达。最后,我们通过组织和细胞实验验证了SIGLEC7在胶质瘤中的作用。具有恶性特征的胶质瘤患者中SIGLEC7表达显着升高。生存分析表明,SIGLEC7 高表达的胶质瘤患者生存率明显较低。基因功能分析显示,SIGLEC7主要参与免疫和炎症反应,与肿瘤相关免疫调节呈强负相关。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巨噬细胞浸润水平之间存在显着的正相关。单细胞分析以及组织和细胞实验证实,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性。 Cox回归分析及生存预测模型的建立表明,SIGLEC7高表达是胶质瘤患者的不利预后因素。 SIGLEC7高表达预示着胶质瘤患者预后不良,且与肿瘤环境中的M2巨噬细胞密切相关。未来,SIGLEC7可能成为胶质瘤免疫治疗的一个有前景的靶点。版权所有©2024 An, Ren, Yuan, Qiu, Wang, Cheng, He, Han, Li and An.
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.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.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.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.Copyright © 2024 An, Ren, Yuan, Qiu, Wang, Cheng, He, Han, Li and An.