Lin Liubing, Que Renye, Wang Jian, Zhu Yi, Liu Xiaolin, Xu Rongzhong
Department of Gastroenterology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Gastroenterology, Shanghai TCM Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Genet. 2022 Jul 25;13:919313. doi: 10.3389/fgene.2022.919313. eCollection 2022.
SLC2A3 is a ferroptosis marker engaged in transmembrane glucose transport. However, the effect of SLC2A3 on the prognosis of patients with cancer remains unclear. This study aimed to explore the prognostic implications of SLC2A3 and its underlying immune mechanisms in gastric cancer. The mRNA expression profiles and corresponding clinical data of patients with gastric cancer were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Differentially expressed genes related to SLC2A3 were identified using the R package "limma." Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, gene set enrichment analysis, and gene set variation analysis were used to explore the underlying mechanisms. The protein-protein and miRNA interaction networks were analyzed using Cytoscape software. Immune cell infiltration was assessed using single-sample gene set enrichment analysis. Univariate and multivariate Cox regression analyses revealed the relationship between SLC2A3 expression and prognosis. SLC2A3 was found to be highly expressed in tumor tissues and was associated with an unfavorable prognosis in patients with gastric cancer. Functional enrichment analysis showed that SLC2A3 is related to cytokine-cytokine receptor interaction, epithelial-mesenchymal transition, T cell receptor signaling pathway, B cell receptor signaling pathway, and immune checkpoints. SLC2A3 is also involved in immune response regulation and is regulated by multiple miRNAs, including miR-195-5p, miR-106a-5p, miR-424-5p, and miR-16-5p. Univariate and multivariate Cox regression analyses indicated that SLC2A3 can be used as an independent prognostic factor for predicting the outcome in patients with gastric cancer. SLC2A3 and related miRNAs are potential prognostic biomarkers and therapeutic targets.
溶质载体家族2成员3(SLC2A3)是一种参与跨膜葡萄糖转运的铁死亡标志物。然而,SLC2A3对癌症患者预后的影响仍不清楚。本研究旨在探讨SLC2A3在胃癌中的预后意义及其潜在的免疫机制。从癌症基因组图谱(The Cancer Genome Atlas)和基因表达综合数据库(Gene Expression Omnibus)下载了胃癌患者的mRNA表达谱和相应的临床数据。使用R包“limma”鉴定与SLC2A3相关的差异表达基因。采用基因本体论(Gene ontology)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes)富集分析、基因集富集分析和基因集变异分析来探索潜在机制。使用Cytoscape软件分析蛋白质-蛋白质和miRNA相互作用网络。采用单样本基因集富集分析评估免疫细胞浸润情况。单因素和多因素Cox回归分析揭示了SLC2A3表达与预后之间的关系。发现SLC2A3在肿瘤组织中高表达,且与胃癌患者的不良预后相关。功能富集分析表明,SLC2A3与细胞因子-细胞因子受体相互作用、上皮-间质转化、T细胞受体信号通路、B细胞受体信号通路和免疫检查点有关。SLC2A3还参与免疫反应调节,并受多种miRNA调控,包括miR-195-5p、miR-106a-5p、miR-424-5p和miR-16-5p。单因素和多因素Cox回归分析表明,SLC2A3可作为预测胃癌患者预后的独立预后因素。SLC2A3及相关miRNA是潜在的预后生物标志物和治疗靶点。