硒蛋白S（SELENOS）是脑低级别胶质瘤的潜在预后生物标志物。

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology Pub Date : 2024-10-04 DOI:10.1016/j.jtemb.2024.127539

Yuetong Wang , Kai Qu , Zengrun Xia , Meng Qi , Xiaoping Du , Zunhua Ke , Rongqiang Zhang

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引用次数: 0

摘要

背景：硒是人体必需的微量营养素，主要以硒半胱氨酸的形式存在于各种硒蛋白中。硒蛋白 S（SELENOS）对人类癌症的发展至关重要。本研究旨在探讨SELENOS基因表达与脑低级胶质瘤（LGG）预后的相关性：方法：通过HPA数据库探讨SELENOS蛋白和mRNA在人体正常组织和肿瘤组织中的表达。利用TCGA和GTEx数据集分析了SELENOS在正常组织和肿瘤组织中的表达差异及其在胶质瘤中的预后意义，并利用CGGA数据集进一步评估了其在中国队列中的预后潜力。此外，还评估了SELENOS表达与肿瘤免疫浸润之间的关联。多变量和单变量Cox模型用于筛选与SELENOS表达相关的临床病理参数。GDSC数据集被用来探索SELENOS与LGG化疗反应之间的联系。建立了SELENOS的蛋白-蛋白相互作用网络。通过Western印迹和qRT-PCR检测SELENOS在LGG细胞系中的表达，并通过常规体外实验确定其功能：结果：与相应的正常组织相比，SELENOS在11种癌症中上调，在10种癌症中下调，并与预后显著相关，尤其是在GBM、LGG和GBMLGG中。此外，它还与 LGG 中的免疫细胞浸润水平呈正相关。多变量和单变量Cox分析证实，SELENOS对LGG预后的影响是年龄和肿瘤分级等因素共同作用的结果。SELENOS的表达与LGG中替莫唑胺的IC50呈显著负相关。我们发现，SELENOS与10种蛋白相互作用，与人体正常组织相比，这些蛋白在LGG中上调。这些相互作用蛋白的表达与SELENOS的表达和LGG的生存/预后呈正相关。体外实验证实了SELENOS在LGG细胞系中的异常表达，siRNA介导的SELENOS敲除降低了LGG细胞的增殖、活力、侵袭和迁移，并诱导细胞凋亡：结论：SELENOS是LGG潜在的预后标志物和治疗靶点，其低表达与LGG的良好预后相关。

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Selenoprotein S (SELENOS) is a potential prognostic biomarker for brain lower grade glioma

Background

Selenium, an essential micronutrient, primarily exists as selenocysteine in various selenoproteins. Selenoprotein S (SELENOS) is crucial in the development of human cancer. This study aimed to explore the correlation between SELENOS gene expression and the prognosis of brain lower-grade glioma (LGG).

Methods

SELENOS protein and mRNA expression in human normal and tumor tissues were explored through the HPA database. SELENOS expression differences between normal and tumor tissues, along with its prognostic significance in gliomas, were analyzed using the TCGA, GTEx datasets, while the CGGA dataset was used to further assess its prognostic potential in a Chinese cohort. The association between SELENOS expression and tumor immune infiltration was also assessed. Multivariate and univariate Cox models were used to screen for clinicopathological parameters associated with SELENOS expression. The GDSC datasets was utilized to explore the connection between SELENOS and chemotherapeutic responses in LGG. A protein-protein interaction network for SELENOS was created. SELENOS expression in LGG cell lines were determined by Western blotting and qRT-PCR, and its functions were ascertained by routine in vitro experiments.

Results

SELENOS was upregulated in 11 cancers and downregulated in 10 cancers relative to the corresponding normal tissues, and correlated significantly with the prognosis, especially for GBM, LGG and GBMLGG. Furthermore, It displayed a positive correlation with immune cell infiltration levels in LGG. Multivariate and Univariate Cox analyses confirmed that the impact of SELENOS on the prognosis of LGG is the combined result of factors such as age and tumor grade. The expression of SELENOS was significantly negatively correlated with temozolomide IC50 in LGG. We found that SELENOS interacts with 10 proteins, which are upregulated in LGG compared to human normal tissues. The expression of these interactors is positively correlated with SELENOS expression and LGG survival/prognosis. In vitro experiments confirmed the aberrant expression of SELENOS in LGG cell lines, and siRNA-mediated knockdown of SELENOS reduced the proliferation, viability, invasion and migration of LGG cells, and induced apoptosis.

Conclusions

SELENOS is a potential prognostic marker and therapeutic target for LGG, and its low expression is associated with favorable prognosis in LGG.

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来源期刊

Journal of Trace Elements in Medicine and Biology 医学-内分泌学与代谢

CiteScore

6.60

自引率

2.90%

发文量

202

审稿时长

85 days

期刊介绍： The journal provides the reader with a thorough description of theoretical and applied aspects of trace elements in medicine and biology and is devoted to the advancement of scientific knowledge about trace elements and trace element species. Trace elements play essential roles in the maintenance of physiological processes. During the last decades there has been a great deal of scientific investigation about the function and binding of trace elements. The Journal of Trace Elements in Medicine and Biology focuses on the description and dissemination of scientific results concerning the role of trace elements with respect to their mode of action in health and disease and nutritional importance. Progress in the knowledge of the biological role of trace elements depends, however, on advances in trace elements chemistry. Thus the Journal of Trace Elements in Medicine and Biology will include only those papers that base their results on proven analytical methods. Also, we only publish those articles in which the quality assurance regarding the execution of experiments and achievement of results is guaranteed.