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与胶质瘤预后和肿瘤免疫微环境相关的铜离子转运蛋白相关基因SLC31A1表达

Cuproptosis-related gene SLC31A1 expression correlates with the prognosis and tumor immune microenvironment in glioma.

发表日期:2023 Aug 23
作者: Jun Wang, Shenglun Li, Yuduo Guo, Chao Zhao, Yujia Chen, Weihai Ning, Jingjing Yang, Hongwei Zhang
来源: Brain Structure & Function

摘要:

铜磷酸诱导细胞死亡是一种新发现的细胞死亡形式, 受一系列基因调控。这些基因被发现能影响肿瘤的进展, 但在胶质母细胞瘤中, 与铜磷酸有关的基因研究较少。使用癌症基因组图谱(TCGA)和基因型-组织表达(GTEx)数据库筛选胶质母细胞瘤和健康组织样本中的SLC31A1基因表达。利用基因表达组学数据库(GEO)和定量实时聚合酶链反应(qPCR)验证结果。使用人类蛋白质图谱(HPA)和美国国家癌症研究所临床蛋白质肿瘤分析联盟(CPTAC)验证我们的结果在蛋白质水平。利用多变量分析和Kaplan-Meier生存曲线来研究SLC31A1基因表达、临床参数和生存率之间的关系。使用搜索作用于互作基因/蛋白质(STRING)在线工具查找与SLC31A1相关的基因和蛋白质。使用肿瘤免疫评估资源(TIMER)数据库进行免疫浸润分析。使用小干扰RNA敲低SLC31A1基因表达, 并使用计数套件-8、流式细胞仪和转彗仪分析细胞增殖、凋亡和迁移。胶质母细胞瘤患者具有更高的SLC31A1表达水平, 且随着世界卫生组织(WHO)分级升高而增加。生存分析表明, SLC31A1基因表达与总生存期(OS)、无进展生存期(PFS)和疾病特异性生存期(DSS)呈负相关。免疫浸润分析显示SLC31A1基因与T辅助2细胞(Th2)、巨噬细胞和M2型巨噬细胞呈正相关, 与浆细胞型树突状细胞(pDCs)、自然杀伤(均质小碎细胞)CD56+细胞和CD8+ T细胞呈负相关。体外减岀(SLC31A1敲低)实验显示SLC31A1敲低抑制了胶质母细胞瘤细胞的增殖和迁移, 促进了凋亡率。SLC31A1基因的表达可以缩短胶质母细胞瘤患者的生存时间。体外研究表明SLC31A1可以促进胶质母细胞瘤细胞的增殖和迁移, 抑制细胞凋亡, 促进肿瘤抑制微环境的形成。©2023。作者。(Note: Translated passage is revised to better align with academic writing style.)
Cuproptosis is a newly discovered form of cell death. It is regulated by a string of genes. The genes are identified to influence the tumor progression, but in glioma, the cuproptosis-related genes are little studied. The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) were used to screen for SLC31A1 gene expression in glioma and healthy tissue samples. The results were validated using the Gene Expression Omnibus (GEO) and quantitative real-time polymerase chain reaction (qPCR). The Human Protein Atlas (HPA) and the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) were used to validate our results at the protein level. Multivariable analysis and Kaplan-Meier survival curves were used to examine the relationship among SLC31A1 gene expression, clinical parameters, and survival rates. The online Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) was used to find the genes and proteins that correlate to SLC31A1. The immune infiltration analysis was performed using the Tumor Immune Estimation Resource (TIMER) databases. Small interfering RNA was used to knock down the SLC31A1 expression, and the cell proliferation, apoptosis, and migration were analyzed using cell counting kit-8, flow cytometry, and transwell. The glioma patients have higher SLC31A1 expression levels, which increase as the World Health Organization (WHO) grade escalates. The survival analysis illustrates that the SLC31A1 gene expression negatively correlates with overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS). The immune infiltration analysis shows the SLC31A1 gene positively correlates with T helper 2 (Th2) cells, macrophages, and M2-type macrophages and negatively correlates with plasmacytoid dendritic cells (pDCs), natural killer (NK) CD56bright cells, and CD8 T cells. The in vitro KD experiment shows the SLC31A1 knockdown depressed the glioma cell proliferation and migration and promoted the apoptosis rate. The SLC31A1 gene expression can shorten the survival time of glioma patients. In vitro study shows that SLC31A1 can promote cell proliferation, and migration, and depress the cell apoptosis of glioma cells. It also can promote the formation of a tumor-suppressive microenvironment.© 2023. The Author(s).