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精胺合酶:低级别胶质瘤的一种潜在预后标志物。

Spermine Synthase : A Potential Prognostic Marker for Lower-Grade Gliomas.

作者信息

Liu Chen, Li Hongqi, Hu Xiaolong, Yan Maohui, Fu Zhiguang, Zhang Hengheng, Wang Yingjie, Du Nan

机构信息

Medical School of Chinese PLA, Beijing, China.

Department of Radiotherapy, Air Force Medical Center, The Fourth Military Medical University, PLA, Beijing, China.

出版信息

J Korean Neurosurg Soc. 2025 Jan;68(1):75-96. doi: 10.3340/jkns.2024.0080. Epub 2024 Nov 5.

DOI:10.3340/jkns.2024.0080
PMID:39492653
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11725456/
Abstract

OBJECTIVE

The objective of this study was to assess the relationship between spermine synthase (SMS) expression, tumor occurrence, and prognosis in lower-grade gliomas (LGGs).

METHODS

A total of 523 LGG patients and 1152 normal brain tissues were included as controls. Mann-Whitney U test was performed to evaluate SMS expression in the LGG group. Functional annotation analysis was conducted to explore the biological processes associated with high SMS expression. Immune cell infiltration analysis was performed to examine the correlation between SMS expression and immune cell types. The association between SMS expression and clinical and pathological features was assessed using Spearman correlation analysis. In vitro experiments were conducted to investigate the effects of overexpressing or downregulating SMS on cell proliferation, apoptosis, migration, invasion, and key proteins in the protein kinase B (AKT)/epithelialmesenchymal transition signaling pathway.

RESULTS

The study revealed a significant upregulation of SMS expression in LGGs compared to normal brain tissues. High SMS expression was associated with certain clinical and pathological features, including older age, astrocytoma, higher World Health Organization grade, poor disease-specific survival, disease progression, non-1p/19q codeletion, and wild-type isocitrate dehydrogenase. Cox regression analysis identified SMS as a risk factor for overall survival. Bioinformatics analysis showed enrichment of eosinophils, T cells, and macrophages in LGG samples, while proportions of dendritic (DC) cells, plasmacytoid DC (pDC) cells, and CD8+ T cells were decreased.

CONCLUSION

High SMS expression in LGGs may promote tumor occurrence through cellular proliferation and modulation of immune cell infiltration. These findings suggest the prognostic value of SMS in predicting clinical outcomes for LGG patients.

摘要

目的

本研究旨在评估精胺合酶(SMS)表达与低级别胶质瘤(LGG)的肿瘤发生及预后之间的关系。

方法

共纳入523例LGG患者和1152例正常脑组织作为对照。采用曼-惠特尼U检验评估LGG组中SMS的表达。进行功能注释分析以探索与高SMS表达相关的生物学过程。进行免疫细胞浸润分析以检测SMS表达与免疫细胞类型之间的相关性。使用Spearman相关分析评估SMS表达与临床和病理特征之间的关联。进行体外实验以研究过表达或下调SMS对细胞增殖、凋亡、迁移、侵袭以及蛋白激酶B(AKT)/上皮-间质转化信号通路中关键蛋白的影响。

结果

研究显示,与正常脑组织相比,LGG中SMS表达显著上调。高SMS表达与某些临床和病理特征相关,包括年龄较大、星形细胞瘤、世界卫生组织分级较高、疾病特异性生存期较差、疾病进展、非1p/19q共缺失以及野生型异柠檬酸脱氢酶。Cox回归分析确定SMS为总生存的危险因素。生物信息学分析显示,LGG样本中嗜酸性粒细胞、T细胞和巨噬细胞富集,而树突状(DC)细胞、浆细胞样DC(pDC)细胞和CD8+T细胞的比例降低。

结论

LGG中高SMS表达可能通过细胞增殖和免疫细胞浸润调节促进肿瘤发生。这些发现提示SMS在预测LGG患者临床结局方面的预后价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b74/11725456/91f161400775/jkns-2024-0080f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b74/11725456/3fbef5b2373f/jkns-2024-0080f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b74/11725456/4c29dffdba0c/jkns-2024-0080f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b74/11725456/9993ac61f29e/jkns-2024-0080f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b74/11725456/d7bdab7d8a1f/jkns-2024-0080f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b74/11725456/1a1a4ff2044d/jkns-2024-0080f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b74/11725456/91f161400775/jkns-2024-0080f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b74/11725456/3fbef5b2373f/jkns-2024-0080f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b74/11725456/4c29dffdba0c/jkns-2024-0080f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b74/11725456/9993ac61f29e/jkns-2024-0080f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b74/11725456/d7bdab7d8a1f/jkns-2024-0080f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b74/11725456/1a1a4ff2044d/jkns-2024-0080f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b74/11725456/91f161400775/jkns-2024-0080f6.jpg

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The combined signatures of telomere and immune cell landscape provide a prognostic and therapeutic biomarker in glioma.端粒和免疫细胞景观的联合特征为胶质瘤提供了一种预后和治疗的生物标志物。
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