Wang Yuetong, Qu Kai, Xia Zengrun, Qi Meng, Du Xiaoping, Ke Zunhua, Zhang Rongqiang
Shaanxi Academy of Traditional Chinese Medicine (Shaanxi Provincial Hospital of Chinese Medicine), Xi'an 710003, PR China.
Ankang R&D Center of Se-enriched Products, Ankang 725000, PR China.
J Trace Elem Med Biol. 2024 Dec;86:127539. doi: 10.1016/j.jtemb.2024.127539. Epub 2024 Oct 4.
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).
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.
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.
SELENOS is a potential prognostic marker and therapeutic target for LGG, and its low expression is associated with favorable prognosis in LGG.
硒是一种必需的微量营养素,主要以硒代半胱氨酸的形式存在于各种硒蛋白中。硒蛋白S(SELENOS)在人类癌症的发生发展中至关重要。本研究旨在探讨SELENOS基因表达与脑低级别胶质瘤(LGG)预后之间的相关性。
通过人类蛋白质图谱(HPA)数据库探究SELENOS蛋白和mRNA在人类正常组织和肿瘤组织中的表达情况。利用癌症基因组图谱(TCGA)、基因型组织表达(GTEx)数据集分析正常组织和肿瘤组织之间SELENOS的表达差异及其在胶质瘤中的预后意义,同时使用中国胶质瘤基因组图谱(CGGA)数据集进一步评估其在中国人群中的预后潜力。还评估了SELENOS表达与肿瘤免疫浸润之间的关联。采用多变量和单变量Cox模型筛选与SELENOS表达相关的临床病理参数。利用基因药物敏感性数据库(GDSC)数据集探究SELENOS与LGG化疗反应之间的联系。构建了SELENOS的蛋白质-蛋白质相互作用网络。通过蛋白质免疫印迹法和定量逆转录聚合酶链反应(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。
相对于相应的正常组织,SELENOS在11种癌症中上调,在10种癌症中下调,且与预后显著相关,尤其是胶质母细胞瘤(GBM)、LGG和胶质母细胞瘤合并低级别胶质瘤(GBMLGG)。此外,它与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预后影响是年龄和肿瘤分级等因素综合作用的结果。SELENOS的表达与LGG中替莫唑胺的半数抑制浓度(IC50)显著负相关。我们发现SELENOS与10种蛋白质相互作用,与人类正常组织相比,这些蛋白质在LGG中上调。这些相互作用蛋白的表达与SELENOS表达及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,小干扰RNA(siRNA)介导的SELENOS敲低降低了LGG细胞的增殖、活力、侵袭和迁移能力,并诱导了细胞凋亡。
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。