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NCAPG2是一种新型的预后生物标志物,可促进低级别胶质瘤中癌症干细胞的维持。

NCAPG2 Is a Novel Prognostic Biomarker and Promotes Cancer Stem Cell Maintenance in Low-Grade Glioma.

作者信息

Ren Wenjun, Yang Shu, Chen Xi, Guo Jishu, Zhao Heng, Yang Ruihan, Nie Zhi, Ding Li, Zhang Lei

机构信息

Department of Cardiovascular Surgery, The First People's Hospital of Yunnan Province, Kunming, China.

Department of Neurology, The First People's Hospital of Yunnan Province, Kunming, China.

出版信息

Front Oncol. 2022 Jul 8;12:918606. doi: 10.3389/fonc.2022.918606. eCollection 2022.

Abstract

Gliomas account for 75% of all primary malignant brain tumors in adults and are associated with high mortality. Mounting evidence has shown that NCAPG2 is differentially expressed in various cancers. However, the prognostic value and immune functions of NCAPG2 in low-grade glioma (LGG) remain unresolved. In the present study, we revealed that NCAPG2 was up-regulated in LGG, and its higher expression was associated with adverse clinical outcomes and poor clinical characteristics, including WHO grade, IDH mutation, 1p/19q codeletion, and primary therapy outcome. The results of the Cox regression analysis revealed that NCAPG2 was an independent factor for the prognosis of low-grade glioma. Meanwhile, we also established a nomogram based on NCAPG2 to predict the 1-, 3-, or 5-year survival in LGG patients. Furthermore, we found that Copy number variation (CNV) and DNA hypomethylation results in its overexpression in LGG. In addition, functional annotation confirmed that NCAPG2 was mainly involved in the immune regulation and WNT signaling pathways. Finally, we determined that increased expression of NCAPG2 was correlated with infiltration levels of various immune cells and immune checkpoint in LGG. Importantly, we found that NCAPG2 was highly expressed in glioma stem cells lines and knockdown of NCAPG2 significantly inhibited the self-renewal ability of GSC. This is the first study to identify NCAPG2 as a new potential prognostic biomarker and characterize the functional roles of NCAPG2 in the progression of LGG, and provides a novel potential diagnostic and therapeutic biomarker for LGG in the future.

摘要

神经胶质瘤占成人所有原发性恶性脑肿瘤的75%,且与高死亡率相关。越来越多的证据表明,NCAPG2在各种癌症中存在差异表达。然而,NCAPG2在低级别胶质瘤(LGG)中的预后价值和免疫功能仍未明确。在本研究中,我们发现NCAPG2在LGG中上调,其高表达与不良临床结局及不良临床特征相关,包括世界卫生组织(WHO)分级、异柠檬酸脱氢酶(IDH)突变、1p/19q共缺失和初始治疗结果。Cox回归分析结果显示,NCAPG2是低级别胶质瘤预后的独立因素。同时,我们还基于NCAPG2建立了列线图,以预测LGG患者的1年、3年或5年生存率。此外,我们发现拷贝数变异(CNV)和DNA低甲基化导致其在LGG中过表达。另外,功能注释证实NCAPG2主要参与免疫调节和WNT信号通路。最后,我们确定NCAPG2表达增加与LGG中各种免疫细胞和免疫检查点的浸润水平相关。重要的是,我们发现NCAPG2在胶质瘤干细胞系中高表达,敲低NCAPG2可显著抑制胶质瘤干细胞的自我更新能力。这是首次将NCAPG2鉴定为一种新的潜在预后生物标志物,并阐述其在LGG进展中的功能作用的研究,为未来LGG提供了一种新的潜在诊断和治疗生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cf9/9309203/977752e6b197/fonc-12-918606-g001.jpg

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