胃癌中免疫相关基因SLC7A7的鉴定与初步验证

Identification and preliminary validation of the immune-related gene SLC7A7 in gastric cancer

  • 摘要:
    目的 通过生物信息学方法筛选胃癌新型免疫相关基因,并在胃癌细胞中进行初步实验验证,以及通过多组学整合揭示SLC7A7在胃癌免疫微环境中的作用。
    方法 从GEO数据库获取胃癌数据集,分析得到差异表达基因。采用STRING软件分析蛋白互作关系,借助Metascape进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。结合TCGA数据,验证基因表达与临床特征的相关性。采用TIMER2.0分析SLC7A7在泛癌中的表达情况。采用Kaplan-Meier Plotter进行生存分析。通过逆转录定量聚合酶链式反应(RT-qPCR)验证SLC7A7在胃癌细胞系中的表达水平。
    结果 SLC7A7在胃癌及多种癌症中高表达,且与不良预后有关。SLC7A7可能通过PI3K-Akt和AMPK信号通路发挥作用。SLC7A7与记忆B细胞、初始B细胞、单核细胞及活化NK细胞呈负相关,与活化CD4+记忆T细胞、γδT细胞、静止NK细胞、未极化巨噬细胞以及M1/M2型巨噬细胞呈正相关。RT-qPCR结果表明, SLC7A7在5种胃癌细胞系(HGC-27、NCI-N87、MKN-45、MKN-74和AGS)中高表达。
    结论 SLC7A7在胃癌细胞系中高表达,且与胃癌患者肿瘤细胞免疫浸润及不良预后相关。

     

    Abstract:
    Objective To screen novel immune-related genes in gastric cancer through bioinformatics approaches, conduct preliminary experimental validation in gastric cancer cells, and elucidate the role of SLC7A7 in the immune microenvironment of gastric cancer via multi-omics integration.
    Methods Gastric cancer datasets were obtained from the GEO database, and differentially expressed genes were identified. Protein-protein interaction networks were analyzed using STRING software, while gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using Metascape. The correlation between gene expression and clinical characteristics was validated using TCGA data. The expression of SLC7A7 across various cancers was analyzed using TIMER2.0. Survival analysis was conducted using Kaplan-Meier Plotter. The expression level of SLC7A7 in gastric cancer cell lines was validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR).
    Results SLC7A7 was highly expressed in gastric cancer and various other cancers, and was associated withpoor prognosis. SLC7A7 may exert its effects through the PI3K-Akt and AMPK signaling pathways. SLC7A7 was negatively correlated with memory B cells, naive B cells, monocytes and activated NK cells, while positively correlated with activated CD4+ memory Tcells, γδ T cells, resting NK cells, unpolarized macrophages and M1/M2 macrophages. RT-qPCR results demonstrated high expression of SLC7A7 in five gastric cancer cell lines (HGC-27, NCI-N87, MKN-45, MKN-74 and AGS).
    Conclusion SLC7A7 is highly expressed in gastric cancer cell lines and is associated with tumor immune infiltration and poor prognosis in gastric cancer patients.

     

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