Fujian Provincial Key Laboratory of Plant Functional Biology, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.
Fujian Provincial Key Laboratory of Plant Functional Biology, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.
World Neurosurg. 2023 Oct;178:e595-e640. doi: 10.1016/j.wneu.2023.07.134. Epub 2023 Aug 4.
The association between SLC10A3 (solute carrier family 10 member 3) and lower grade glioma (LGG) remains unclear.
We used public databases and bioinformatics analysis to analyze SLC10A3. These included The Cancer Genome Atlas, Genotype-Tissue Expansion, Chinese Glioma Genome Atlas, Human Protein Atlas, GeneCards, cBioPortal, Search Tool for the Retrieval of Interacting Genes/Proteins, Gene Expression Profiling Interactive Analysis, Tumor Immune Estimation Resource, Tumor-Immune System Interaction Database, receiver operating characteristic curve analysis, Kaplan-Meier analysis, Cox analysis, nomograms, calibration plots, gene ontology/Kyoto Encyclopedia of Genes and Genomes enrichment analysis, gene set enrichment analysis, single-sample gene set enrichment analysis, and Spearman's correlation analysis.
SLC10A3 was upregulated in adrenocortical carcinoma, glioblastoma, and LGG and was associated with good overall survival (OS) in adrenocortical carcinoma and poor OS in LGG and glioblastoma. SLC10A3 was increased with increased World Health Organization grade, upregulated in isocitrate dehydrogenase-wild type, 1p/19q (chromosome arms 1p and 19q) non-co-deleted, and higher in astrocytoma. Patients with LGG were grouped by the occurrence of the clinical outcome endpoints (i.e., OS, disease-specific survival [DSS], and progression-free interval events). Genetic alterations in SLC10A3 were associated with poor progression-free survival in LGG. Most of clinical characteristics were associated with the SLC10A3 expression level. SLC10A3 with diagnostic and prognostic value (OS, DSS, and progression-free interval) was an independent prognostic factor in LGG. Moreover, Nomograms (WHO grade, 1p/19q codeletion, age and SLC10A3) had moderately accurate predictive for OS and DSS. Functional analysis showed that SLC10A3 might participate in the transport of multiple substances, neurogenic signaling, immune response, and programmed cell death in LGG. SLC10A3 correlated with immune infiltration in LGG and moderately correlated with the gene signature of pyroptosis, lysosome-dependent cell death, necroptosis, apoptosis, ferroptosis, alkaliptosis, and autophagy-dependent cell death.
SLC10A3 is a potential diagnostic and prognostic biomarker for LGG and might be associated with substance transport, neurogenic signaling, immune infiltration, and programmed cell death in LGG.
SLC10A3（溶质载体家族 10 成员 3）与低级别胶质瘤（LGG）之间的关联尚不清楚。
我们使用公共数据库和生物信息学分析来分析 SLC10A3。这些分析包括癌症基因组图谱（TCGA）、基因-组织扩展（Genotype-Tissue Expansion）、中国胶质瘤基因组图谱（CGGA）、人类蛋白质图谱（Human Protein Atlas）、GeneCards、cBioPortal、用于检索相互作用基因/蛋白质的工具（Search Tool for the Retrieval of Interacting Genes/Proteins）、基因表达谱交互分析（Gene Expression Profiling Interactive Analysis）、肿瘤免疫估计资源（Tumor Immune Estimation Resource）、肿瘤-免疫系统相互作用数据库（Tumor-Immune System Interaction Database）、受试者工作特征曲线分析（Receiver Operating Characteristic Curve Analysis）、Kaplan-Meier 分析（Kaplan-Meier Analysis）、Cox 分析（Cox Analysis）、列线图（Nomograms）、校准图（Calibration Plots）、基因本体论/京都基因与基因组百科全书富集分析（Gene Ontology/Kyoto Encyclopedia of Genes and Genomes Enrichment Analysis）、基因集富集分析（Gene Set Enrichment Analysis）、单样本基因集富集分析（Single-Sample Gene Set Enrichment Analysis）和 Spearman 相关分析（Spearman's Correlation Analysis）。
SLC10A3 在肾上腺皮质癌、胶质母细胞瘤和 LGG 中上调，并与肾上腺皮质癌的总体生存（Overall Survival，OS）良好和 LGG 和胶质母细胞瘤的 OS 不良相关。SLC10A3 随着世界卫生组织（World Health Organization，WHO）分级的增加而增加，在异柠檬酸脱氢酶野生型（Isocitrate Dehydrogenase-Wild Type）、1p/19q（染色体臂 1p 和 19q）非共缺失（Non-Codeletion）中上调，并在星形细胞瘤中更高。根据临床结局终点（即 OS、疾病特异性生存 [Disease-Specific Survival，DSS] 和无进展间隔事件），将 LGG 患者分为两组。SLC10A3 的遗传改变与 LGG 的无进展生存期不良相关。大多数临床特征与 SLC10A3 的表达水平相关。具有诊断和预后价值（OS、DSS 和无进展间隔）的 SLC10A3 是 LGG 的独立预后因素。此外，Nomograms（WHO 分级、1p/19q 缺失、年龄和 SLC10A3）对 OS 和 DSS 具有中等准确的预测能力。功能分析表明，SLC10A3 可能参与 LGG 中多种物质的转运、神经发生信号、免疫反应和程序性细胞死亡。SLC10A3 与 LGG 中的免疫浸润相关，与细胞焦亡、溶酶体依赖性细胞死亡、坏死性凋亡、细胞凋亡、铁死亡、碱中毒和自噬依赖性细胞死亡的基因特征中度相关。
SLC10A3 是 LGG 的潜在诊断和预后生物标志物，可能与 LGG 中的物质转运、神经发生信号、免疫浸润和程序性细胞死亡有关。
