胶质母细胞瘤中FNDC4的预后价值与巨噬细胞极化的相关性。

Correlation of the prognostic value of FNDC4 in glioblastoma with macrophage polarization.

作者信息

Li Hongwu, Yan Xiaofei, Ou Shaowu

机构信息

Department of Neurosurgery, First Affiliated Hospital of China Medical University, Shenyang, China.

Department of Neurosurgery, The First People's Hospital of Nantong City (Affiliated Hospital 2 of Nantong University), Nantong, China.

出版信息

Cancer Cell Int. 2022 Sep 2;22(1):273. doi: 10.1186/s12935-022-02688-7.

DOI:10.1186/s12935-022-02688-7

PMID:36056336

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9440505/

Abstract

BACKGROUND

Glioblastoma is among the most malignant tumors in the central nervous system and characterized by strong invasion and poor prognosis. Fibronectin type III domain-containing 4 (FNDC4) plays various important roles in the human body, including participating in cellular metabolism and inflammatory responses to cardiovascular diseases, influencing immune cells, and exerting anti-inflammatory effects; however, the role of FNDC4 in glioblastoma has not been reported.

METHODS

In this study, bioinformatics databases, including TCGA, CGGA, GTEx, and TIMER, were used to analyze the differential expression of FNDC4 genes and cell survival, in addition to investigating its relationship with immune cell infiltration. Additionally, we overexpressed FNDC4 in glioblastoma cell lines U87 and U251 by lentiviral transfection and detected changes in proliferation, cell cycle progression, and apoptosis. Following collection of monocytes from the peripheral blood of healthy individuals and transformation into M0 macrophages, we performed flow cytometry to detect the polarizing effect of exogenous FNDC4, as well as the effect of FNDC4-overexpressing glioblastoma cells on macrophage polarization in a co-culture system.

RESULTS

We identified that significantly higher FNDC4 expression in glioblastoma tissue relative to normal brain tissue was associated with worse prognosis. Moreover, we found that FNDC4 overexpression in U87 and U251 cells resulted in increased proliferation and affected the S phase of tumor cells, whereas cell apoptosis remained unchanged. Furthermore, exogenous FNDC4 inhibited the M1 polarization of M0 macrophages without affecting M2 polarization; this was also observed in glioblastoma cells overexpressing FNDC4.

CONCLUSIONS

FNDC4 expression is elevated in glioblastoma, closely associated with poor prognosis, and promoted the proliferation of glioblastoma cells, affected the S phase of tumor cells while inhibiting macrophage polarization.

摘要

背景

胶质母细胞瘤是中枢神经系统中最恶性的肿瘤之一，具有强侵袭性和预后差的特点。含III型纤连蛋白结构域蛋白4（FNDC4）在人体中发挥多种重要作用，包括参与细胞代谢和对心血管疾病的炎症反应、影响免疫细胞以及发挥抗炎作用；然而，FNDC4在胶质母细胞瘤中的作用尚未见报道。

方法

在本研究中，除了研究FNDC4基因的差异表达及其与免疫细胞浸润的关系外，还利用包括TCGA、CGGA、GTEx和TIMER在内的生物信息学数据库分析其与细胞存活的关系。此外，我们通过慢病毒转染在胶质母细胞瘤细胞系U87和U251中过表达FNDC4，并检测其增殖、细胞周期进程和凋亡的变化。从健康个体外周血中收集单核细胞并将其转化为M0巨噬细胞后，我们进行流式细胞术检测外源性FNDC4的极化作用，以及在共培养系统中过表达FNDC4的胶质母细胞瘤细胞对巨噬细胞极化的影响。

结果

我们发现，相对于正常脑组织，胶质母细胞瘤组织中FNDC4表达显著升高与较差的预后相关。此外，我们发现U87和U251细胞中FNDC4过表达导致增殖增加并影响肿瘤细胞的S期，而细胞凋亡保持不变。此外，外源性FNDC4抑制M0巨噬细胞向M1极化，而不影响M2极化；在过表达FNDC4的胶质母细胞瘤细胞中也观察到了这一现象。