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PTBP1 是一种新型的胶质瘤预后不良因素。

PTBP1 is a Novel Poor Prognostic Factor for Glioma.

机构信息

Department of Emergency, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412007, China.

Department of Trauma Center, The Affiliated Zhuzhou Hospital of Xiangya Medical College CSU, Zhuzhou 412007, China.

出版信息

Biomed Res Int. 2022 Mar 8;2022:7590997. doi: 10.1155/2022/7590997. eCollection 2022.

Abstract

OBJECTIVE

Polypyrimidine tract-binding protein 1 (PTBP1) is an RNA-binding protein, which plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. However, little was known about the correlation between PTBP1 and glioma and its prognostic significance in glioma patients. Our aim was to investigate the expression, functional role, and prognostic value of PTBP1 in glioma.

METHODS

We explored the expression of PTBP1 protein using immunohistochemistry in 150 adult malignant glioma tissues and 20 normal brain tissues and evaluated its association with clinicopathological parameters by chi-square test. Kaplan-Meier method was used to evaluate the prognostic effect of PTBP1 in glioma. Univariate/multivariate Cox analyses were used to identify independent prognostic factors. Transcriptional regulation network was constructed based on differentially expressed genes (DEGs) of PTBP1 from TCGA/CGGA database. GO and KEGG enrichment analyses were used to explore the function and pathways of DEGs.

RESULTS

Out of the 150 malignant glioma tissues (60 LGG and 90 GBMs) and 20 normal brain tissues in our cohort, PTBP1 protein was high expressed in glioma tissues (79/150, 52.7%), but no expression was detected in normal brain tissues (0/20, 0%). The expression of PTBP1 was significantly higher in GBMs ( < 0.001). More than half of GBMs (62/90, 68.9%) were PTBP1 high expression. Chi-square test showed that the expression of PTBP1 was correlated with patient age, WHO grade, Ki-67 index, and IDH status. High expression of PTBP1 was significantly associated with poor prognosis in glioma, and it was an independent risk factor in glioma patients. Furthermore, we shed light on the underlying mechanism of PTBP1 by constructing a miR-218-TCF3-PTBP1 transcriptional network in glioma.

CONCLUSION

PTBP1 was high expressed in glioma, and it significantly correlated with poor prognosis, suggesting a potential therapeutic target for glioma, particularly for GBM.

摘要

目的

多嘧啶核苷酸结合蛋白 1(PTBP1)是一种 RNA 结合蛋白,在 mRNA 前体剪接和调控可变剪接事件中发挥作用。然而,PTBP1 与神经胶质瘤的相关性及其在神经胶质瘤患者中的预后意义知之甚少。我们的目的是研究 PTBP1 在神经胶质瘤中的表达、功能作用和预后价值。

方法

我们使用免疫组织化学法检测了 150 例成人恶性神经胶质瘤组织和 20 例正常脑组织中 PTBP1 蛋白的表达,并通过卡方检验评估其与临床病理参数的相关性。Kaplan-Meier 法用于评估 PTBP1 在神经胶质瘤中的预后作用。单因素/多因素 Cox 分析用于确定独立的预后因素。基于 TCGA/CGGA 数据库中 PTBP1 的差异表达基因(DEGs)构建转录调控网络。GO 和 KEGG 富集分析用于探索 DEGs 的功能和途径。

结果

在我们的队列中,150 例恶性神经胶质瘤组织(60 例 LGG 和 90 例 GBM)和 20 例正常脑组织中,PTBP1 蛋白在神经胶质瘤组织中高表达(79/150,52.7%),但在正常脑组织中无表达(0/20,0%)。PTBP1 在 GBM 中的表达显著升高(<0.001)。超过一半的 GBM(62/90,68.9%)为 PTBP1 高表达。卡方检验显示,PTBP1 的表达与患者年龄、WHO 分级、Ki-67 指数和 IDH 状态相关。PTBP1 的高表达与神经胶质瘤患者的不良预后显著相关,是神经胶质瘤患者的独立危险因素。此外,我们通过构建神经胶质瘤中 miR-218-TCF3-PTBP1 转录网络,揭示了 PTBP1 的潜在作用机制。

结论

PTBP1 在神经胶质瘤中高表达,与不良预后显著相关,提示其可能成为神经胶质瘤的潜在治疗靶点,特别是 GBM。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5076/8923792/07c77475a48f/BMRI2022-7590997.001.jpg

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