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过氧化物酶是通过生物信息学方法和实验验证发现的胶质母细胞瘤新型潜在标志物

英文原题:Peroxidase is a novel potential marker in glioblastoma through bioinformatics method and experimental validation.

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Peroxidase is a novel potential marker in glioblastoma through bioinformatics method and experimental validation.

PubMed 2022/08/31(内容时间) Front Genet Q2 · IF 3(JCR 2025)

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中文摘要

过氧化物酶(PXDN)是一种特异性细胞外基质(ECM)相关蛋白,已被确定为多种肿瘤的肿瘤指标和治疗靶点。然而,PXDN在胶质母细胞瘤(GBM)中的预后表现和临床意义仍不清楚。

在此,我们评估了来自TCGA和CGGA数据库中GBM病例的PXDN表达模式及其对预后的影响。与正常对照相比,PXDN在GBM样本中上调。PXDN高表达是GBM的不良预后指标。进行单细胞RNA分析以检测PXDN的细胞定位。

我们还建立了PPI网络以探索与PXDN相互作用的蛋白,包括TSKU、COL4A1和COL5A1。一致地,功能富集分析显示,在PXDN高表达的GBM病例中富集了若干癌症标志,如上皮-间质转化(EMT)、脂肪酸代谢、糖酵解、缺氧、炎症反应和Wnt/beta-catenin信号通路。接下来,本研究分析了PXDN表达与免疫细胞浸润的关联。PXDN表达与静息NK细胞、调节性T细胞、M0巨噬细胞、单核细胞和嗜酸性粒细胞的浸润程度成正比。通过PXDN相关免疫调节剂进一步评估了PXDN对免疫的作用。

此外,还鉴定了四个与PXDN共表达的预后相关lncRNA。最后,我们通过体外实验观察到,PXDN缺失抑制GBM细胞增殖和迁移。

我们的数据表明,PXDN有潜力成为一种强大的预后生物标志物,这可能为开发GBM治疗靶点提供基础。

展开英文摘要原文

Peroxidase (PXDN), a specific extracellular matrix (ECM)-associated protein, has been determined as a tumor indicator and therapeutic target in various tumors.

However, the effects of PXDN in prognostic performance and clinical implications in glioblastoma multiforme (GBM) remains unknown.

Here, we assessed PXDN expression pattern and its performance on prognosis among GBM cases from TCGA and CGGA databases. PXDN was up-regulated within GBM samples in comparison with normal control. High PXDN expression was a dismal prognostic indicator in GBM. Single cell RNA analysis was conducted to detect the cell localization of PXDN.

We also set up a PPI network to explore the interacting protein associated with PXDN, including TSKU, COL4A1 and COL5A1. Consistently, functional enrichment analysis revealed that several cancer hallmarks were enriched in the GBM cases with high PXDN expression, such as epithelial-mesenchymal transition (EMT), fatty acid metabolism, glycolysis, hypoxia, inflammatory response, and Wnt/beta-catenin signaling pathway.

Next, this study analyzed the association of PXDN expression and immunocyte infiltration. PXDN expression was in direct proportion to the infiltrating degrees of NK cells resting, T cells regulatory, M0 macrophage, monocytes and eosinophils. The roles of PXDN on immunity were further estimated by PXDN-associated immunomodulators.

In addition, four prognosis-related lncRNAs co-expressed with PXDN were identified.

Finally, we observed that PXDN depletion inhibits GBM cell proliferation and migration by in vitro experiments.

Our data suggested that PXDN has the potential to be a powerful prognostic biomarker, which might offer a basis for developing therapeutic targets for GBM.

论文信息

作者
Shi W、Ding W、Zhao Z、Wang R、Wang F、Tang Y、Zhu J、Su C
第一作者单位
Nantong Hospital of Traditional Chinese Medicine, Affiliated Traditional Chinese Medicine Hospital of Nantong University, Nantong, China.China
通讯作者单位
Department of Pathology, Affiliated Hospital of Nantong University, Nantong, China.China
期刊
Frontiers in genetics2022
原文标识
PubMed 36118855 · DOI 10.3389/fgene.2022.990344