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β3GNT9作为胶质母细胞瘤的预后生物标志物及其与胶质母细胞瘤免疫浸润、迁移和侵袭的关系。

β3GNT9 as a prognostic biomarker in glioblastoma and its association with glioblastoma immune infiltration, migration and invasion.

作者信息

Luo YingHao, Wang Kan, Zhan Lu, Zeng Fanyue, Zheng Jie, Chen Sijing, Duan Xingbang, Ju Donghui

机构信息

Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Front Oncol. 2023 Sep 12;13:1214413. doi: 10.3389/fonc.2023.1214413. eCollection 2023.

Abstract

BACKGROUND

Studies have shown that the immune infiltration of tumor microenvironment is related to the prognosis of glioblastoma, which is characterized by high heterogeneity, high recurrence rate and low survival rate. To unravel the role of β1,3-N-acetylglucosaminyltransferase-9 (β3GNT9) in the progression of glioblastoma, this study identifies the value of β3GNT9 as a prognostic biomarker in glioblastoma, and investigates the relationship between β3GNT9 expression and glioblastoma immune infiltration, migration and invasion.

METHODS

β3GNT9 expression in glioblastoma was analyzed using the GEPIA database. The clinical features of glioblastoma were screened out from the TCGA database. The relationship between β3GNT9 expression and clinical features was analyzed. The relationship between β3GNT9 and the prognosis of glioblastoma was evaluated through univariate and multivariate COX regression analyses, and the survival analysis was conducted using the Kaplan-Meier method. GSEA was employed to predict the signaling pathway of β3GNT9 in glioblastoma. The correlation between β3GNT9 and tumor immune infiltration was analyzed using the related modules of CIBERSORT and TIMER. A172, U87MG and U251 cell lines were selected to verify β3GNT9 expression . The effects of β3GNT9 on the migration and invasion of glioblastoma were investigated through cell scratch and invasion assays.

RESULTS

β3GNT9 expression in glioblastoma group was significantly higher than that in normal brain tissue group (<0.05). The overall survival rate in high β3GNT9 expression group was significantly lower than that in low β3GNT9 expression group (<0.05). Regression analyses suggested that β3GNT9, involved primarily in glucosamine degradation and extracellular matrix receptor interaction, could be an independent prognostic factor for glioblastoma. CIBERSORT and GEPIA database analyses showed that β3GNT9 was correlated with tumor infiltrating immune cells such as T follicular helper cells, activating natural killer cells, monocytes, macrophages, and eosinophils, thus affecting the immune microenvironment of glioblastoma. Cell experiments confirmed that β3GNT9 was highly expressed in A172, U87MG and U251 cell lines (<0.05), and promoted the migration and invasion of glioblastoma (<0.05).

CONCLUSION

The increased expression of β3GNT9 in glioblastoma can affect the immune microenvironment of glioblastoma and promote its migration and invasion. β3GNT9 can be used as a potential independent prognostic biomarker for patients with glioblastoma.

摘要

背景

研究表明,肿瘤微环境的免疫浸润与胶质母细胞瘤的预后相关,胶质母细胞瘤具有高度异质性、高复发率和低生存率的特点。为了阐明β1,3-N-乙酰葡糖胺基转移酶-9(β3GNT9)在胶质母细胞瘤进展中的作用,本研究确定了β3GNT9作为胶质母细胞瘤预后生物标志物的价值,并研究了β3GNT9表达与胶质母细胞瘤免疫浸润、迁移和侵袭之间的关系。

方法

使用GEPIA数据库分析胶质母细胞瘤中β3GNT9的表达。从TCGA数据库中筛选出胶质母细胞瘤的临床特征。分析β3GNT9表达与临床特征之间的关系。通过单因素和多因素COX回归分析评估β3GNT9与胶质母细胞瘤预后的关系,并使用Kaplan-Meier方法进行生存分析。采用GSEA预测β3GNT9在胶质母细胞瘤中的信号通路。使用CIBERSORT和TIMER的相关模块分析β3GNT9与肿瘤免疫浸润之间的相关性。选择A172、U87MG和U251细胞系验证β3GNT9的表达。通过细胞划痕和侵袭实验研究β3GNT9对胶质母细胞瘤迁移和侵袭的影响。

结果

胶质母细胞瘤组中β3GNT9的表达明显高于正常脑组织组(<0.05)。高β3GNT9表达组的总生存率明显低于低β3GNT9表达组(<0.05)。回归分析表明,主要参与氨基糖降解和细胞外基质受体相互作用的β3GNT9可能是胶质母细胞瘤的独立预后因素。CIBERSORT和GEPIA数据库分析表明,β3GNT9与肿瘤浸润免疫细胞如滤泡辅助性T细胞、活化自然杀伤细胞、单核细胞、巨噬细胞和嗜酸性粒细胞相关,从而影响胶质母细胞瘤的免疫微环境。细胞实验证实,β3GNT9在A172、U87MG和U251细胞系中高表达(<0.05),并促进胶质母细胞瘤的迁移和侵袭(<0.05)。

结论

胶质母细胞瘤中β3GNT9表达增加可影响胶质母细胞瘤的免疫微环境并促进其迁移和侵袭。β3GNT9可作为胶质母细胞瘤患者潜在的独立预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1112/10523150/79f8075165c0/fonc-13-1214413-g001.jpg

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