四跨膜蛋白 6 的诊断和预后意义及其在促进胶质瘤进展中的作用。

Diagnostic and prognostic significance of tetraspanin 6 and its role in facilitating glioma progression.

机构信息

Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China.

State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an, 710032, China.

出版信息

Eur J Med Res. 2024 Oct 29;29(1):522. doi: 10.1186/s40001-024-02119-5.

DOI:10.1186/s40001-024-02119-5

PMID:39472973

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11520469/

Abstract

BACKGROUND

Several tetraspanin (TSPAN) proteins have been implicated in tumorigenesis and disease progression. However, the precise function of tetraspanin 6 (TSPAN6) in glioma remains unclear.

METHODS

Integrated raw data from the Tumor Genome Atlas (TCGA) and Gene Expression Profiling (GEO) databases were processed using R4.2.1. Bioinformatic methods were used to analyze the gene expression levels of TSPAN6 in both glioma and normal brain tissues, correlating them with clinical characteristics. Additionally, the predictive value of TSPAN6 in relation to the immune checkpoint blockade (ICB) therapy response was assessed. In vitro experiments were conducted to investigate the effects of TSPAN6 knockdown on glioma cell proliferation, migration, cell cycle regulation, and macrophage recruitment.

RESULTS

TSPAN6 expression was significantly upregulated in glioma tissues compared to normal tissues. Elevated TSPAN6 expression is strongly correlated with unfavorable clinical characteristics in gliomas. Bioinformatic analyses revealed a significant correlation between elevated TSPAN6 expression and reduced overall survival. Additionally, TSPAN6 was co-expressed with several immune checkpoint genes and revealed a prognostic value in the context of ICB therapy. Functional enrichment analysis revealed the involvement of TSPAN6 in cell-cycle regulation. Furthermore, TSPAN6 expression positively correlated with macrophage and neutrophil infiltration. In vitro experiments confirmed that the downregulation of TSPAN6 inhibited U251 cell proliferation, disrupted the cell cycle, diminished migratory capabilities, and reduced the recruitment of macrophages.

CONCLUSION

Our findings emphasize its potential as both a diagnostic and therapeutic target as well as a predictor of immune therapy response in gliomas.

摘要

背景

几种四跨膜蛋白（TSPAN）已被牵涉到肿瘤发生和疾病进展中。然而，四跨膜蛋白 6（TSPAN6）在神经胶质瘤中的确切功能仍不清楚。

方法

使用 R4.2.1 处理来自肿瘤基因组图谱（TCGA）和基因表达谱（GEO）数据库的综合原始数据。使用生物信息学方法分析 TSPAN6 在神经胶质瘤和正常脑组织中的基因表达水平，并将其与临床特征相关联。此外，评估了 TSPAN6 与免疫检查点阻断（ICB）治疗反应的预测价值。进行体外实验以研究 TSPAN6 敲低对神经胶质瘤细胞增殖、迁移、细胞周期调控和巨噬细胞募集的影响。

结果

与正常组织相比，TSPAN6 在神经胶质瘤组织中表达显著上调。TSPAN6 的高表达与神经胶质瘤中不利的临床特征密切相关。生物信息学分析显示，TSPAN6 表达升高与总生存期缩短显著相关。此外，TSPAN6 与几种免疫检查点基因共表达，并在 ICB 治疗的背景下具有预后价值。功能富集分析显示 TSPAN6 参与细胞周期调控。此外，TSPAN6 的表达与巨噬细胞和中性粒细胞浸润呈正相关。体外实验证实，下调 TSPAN6 抑制 U251 细胞增殖、破坏细胞周期、降低迁移能力，并减少巨噬细胞的募集。