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原胶原蛋白 C 蛋白酶增强蛋白是胶质母细胞瘤的一个预后因素,通过调节多种与肿瘤相关的通路和免疫微环境促进胶质母细胞瘤的发展。

Procollagen C-protease enhancer protein is a prognostic factor for glioma and promotes glioma development by regulating multiple tumor-related pathways and immune microenvironment.

机构信息

Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

出版信息

Int J Immunopathol Pharmacol. 2022 Jan-Dec;36:3946320221104548. doi: 10.1177/03946320221104548.

Abstract

OBJECTIVES

Glioma is a common type of brain tumor with high incidence and mortality rates. Procollagen C-protease enhancer protein (PCOLCE) has been shown to regulate tumor growth and metastasis in several cancers. However, the role of PCOLCE in glioma is unknown. This study aims to assess the association between PCOLCE and prognosis of glioma, and investigated the potential mechanisms.

METHODS

The prognostic value of PCOLCE was determined using data from nine publicly available glioma cohorts. We also investigated the relationship between PCOLCE and glioma immune microenvironment and predicted response to immunotherapy based on the expression levels of PCOLCE. The potential roles of PCOLCE in glioma were also explored and validated in cell experiment.

RESULTS

Survival analysis suggested that high-PCOLCE expression was associated with poor prognosis in glioma. Upregulation of PCOLCE enhanced an immune suppressive microenvironment in glioma by regulating immunocyte infiltration and Cancer-Immunity Cycle. Cox and ROC analysis revealed that PCOLCE was a prognostic factor for glioma and could be used to predict survival of the patients. Patients with low-PCOLCE expression were more likely to respond to Immunotherapy with ICI (immune checkpoint inhibitor) and survive longer. Enrichment analysis showed that PCOLCE was associated with multiple tumor-related pathways. Finally, we demonstrated that the knockdown of PCOLCE inhibited glioma development by regulating cell cycle and promoting apoptosis in in vitro experiments.

CONCLUSION

PCOLCE promotes glioma progression by regulating multiple tumor-related pathways and immune microenvironment and can be used as a prognostic factor for glioma.

摘要

目的

脑胶质瘤是一种常见的脑肿瘤,具有较高的发病率和死亡率。脯氨酰寡肽酶增强子蛋白(PCOLCE)已被证明在多种癌症中调节肿瘤生长和转移。然而,PCOLCE 在脑胶质瘤中的作用尚不清楚。本研究旨在评估 PCOLCE 与脑胶质瘤预后的关系,并探讨其潜在机制。

方法

使用来自 9 个公开可用的脑胶质瘤队列的数据确定 PCOLCE 的预后价值。我们还根据 PCOLCE 的表达水平研究了 PCOLCE 与脑胶质瘤免疫微环境的关系以及对免疫治疗的反应预测。还在细胞实验中探索和验证了 PCOLCE 在脑胶质瘤中的潜在作用。

结果

生存分析表明,高 PCOLCE 表达与脑胶质瘤预后不良相关。PCOLCE 的上调通过调节免疫细胞浸润和癌症免疫循环,增强了脑胶质瘤中的免疫抑制微环境。Cox 和 ROC 分析显示,PCOLCE 是脑胶质瘤的预后因素,可用于预测患者的生存情况。PCOLCE 低表达的患者对免疫治疗(ICI,免疫检查点抑制剂)更敏感,存活时间更长。富集分析表明,PCOLCE 与多种肿瘤相关通路有关。最后,我们在体外实验中证明,通过调节细胞周期和促进细胞凋亡,敲低 PCOLCE 可抑制脑胶质瘤的发展。

结论

PCOLCE 通过调节多种肿瘤相关通路和免疫微环境促进脑胶质瘤的进展,可以作为脑胶质瘤的预后因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e60c/9158419/fa7cc7dd60c1/10.1177_03946320221104548-fig1.jpg

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