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FOXD3-AS1在胶质瘤患者中的预后价值及免疫浸润模式

Prognostic value and immune-infiltration pattern of FOXD3-AS1 in patients with glioma.

作者信息

Chen Zhenhua, Zhang Yi, Feng Sujuan, Yuan Jiaqi, Shi Dongliang, Wang Yong, Li Yongdong, Dong Jun

机构信息

Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou, China.

Department of Neurosurgery, Affiliated Hospital 2 of Nantong University and Affiliated Hospital of Kangda College of Nanjing Medical University, Nantong, China.

出版信息

Front Pharmacol. 2023 Apr 4;14:1162309. doi: 10.3389/fphar.2023.1162309. eCollection 2023.

DOI:10.3389/fphar.2023.1162309
PMID:37081968
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10110859/
Abstract

Gliomas are difficult-to-treat brain tumors due to their aggressive nature, rapid proliferation, and high invasiveness (Zhang et al., J Cell Biochem, 2019, 120 (9), 15106-15118; Ge et al., Int J Biochem Cell Biol, 2021, 139, 106054). FOXD3-AS1 has been identified as an emerging potential target for tumor prediction and treatment in many studies (Qin et al., Front Oncol, 2021, 11, 688027). However, the utility of FOXD3-AS1 has not been reported in glioma patients (Li et al., Cancer Manag Res, 2021, 13, 9037-9048). The differential profiles of FOXD3-AS1 in TCGA-GBMLGG database were analyzed across clinical subgroups. The analysis of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) revealed that a high level of FOXD3-AS1 was associated with a poor prognosis and survival outcome. Based on the Cox regression analysis, FOXD3-AS1 was found to be a high-risk factor for glioma that affects prognosis outcomes independently. More importantly, because oxidative stress is closely linked to glioma prognosis, we focused on the potential mechanisms of six oxidative stress co-expressed genes with FOXD3-AS1. In addition, the predictive value of FOXD3-AS1 was determined for each clinical subgroup status. The ROC curve results showed that FOXD3-AS1 had a good predictive performance. A stratified clinicopathological subgroup analysis revealed that high expression of FOXD3-AS1 is associated with a poor prognosis. This also indicates a link between FOXD3-AS1 and tumorigenesis and prognosis, which has potential application value. Furthermore, the immune cell infiltration of FOXD3-AS1 and the signal marker correlation suggested that immune cell infiltration differed significantly between immune cell subsets. To the best of our knowledge, this is the first report to investigate FOXD3-AS1 in glioma and how it may modulate GBM and LGG immune microenvironments. Furthermore, FOXD3-AS1 was detected in tumor and paraneoplastic tissues using RT-qPCR. Transwell analysis verified the migration and invasion of the FOXD3-AS1 knockout group to a certain extent. In conclusion, FOXD3-AS1 can be used as a prognostic indicator for GBM and LGG, and it is closely related to immune infiltration and response to oxidative stress, which may contribute to the advancement of glioma immunotherapy research.

摘要

胶质瘤因其侵袭性、快速增殖和高侵袭性而难以治疗（Zhang等人，《细胞生物化学杂志》，2019年，120(9)，15106 - 15118；Ge等人，《国际生物化学与细胞生物学杂志》，2021年，139，106054）。在许多研究中，FOXD3 - AS1已被确定为肿瘤预测和治疗的一个新兴潜在靶点（Qin等人，《肿瘤学前沿》，2021年，11，688027）。然而，FOXD3 - AS1在胶质瘤患者中的效用尚未见报道（Li等人，《癌症管理与研究》，2021年，13，9037 - 9048）。在TCGA - GBMLGG数据库中分析了FOXD3 - AS1在不同临床亚组中的差异特征。对总生存期（OS）、疾病特异性生存期（DSS）和无进展生存期（PFI）的分析表明，高水平的FOXD3 - AS1与不良预后和生存结果相关。基于Cox回归分析，发现FOXD3 - AS1是胶质瘤的一个高危因素，可独立影响预后结果。更重要的是，由于氧化应激与胶质瘤预后密切相关，我们聚焦于与FOXD3 - AS1共表达的六个氧化应激基因的潜在机制。此外，还确定了FOXD3 - AS1对每个临床亚组状态的预测价值。ROC曲线结果显示FOXD3 - AS1具有良好的预测性能。分层临床病理亚组分析显示，FOXD3 - AS1高表达与不良预后相关。这也表明FOXD3 - AS1与肿瘤发生和预后之间存在联系，具有潜在的应用价值。此外，FOXD3 - AS1的免疫细胞浸润及信号标志物相关性表明，免疫细胞亚群之间的免疫细胞浸润存在显著差异。据我们所知，这是首次在胶质瘤中研究FOXD3 - AS1及其如何调节胶质母细胞瘤（GBM）和低级别胶质瘤（LGG）免疫微环境的报告。此外，使用RT - qPCR在肿瘤和瘤旁组织中检测到了FOXD3 - AS1。Transwell分析在一定程度上验证了FOXD3 - AS1敲除组的迁移和侵袭能力。总之，FOXD3 - AS1可作为GBM和LGG的预后指标，且与免疫浸润及对氧化应激的反应密切相关，这可能有助于推动胶质瘤免疫治疗研究的进展。

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