Wu Zhenhai, Liu Pengyuan, Zhang Ganlu
Department of Oncology, Zhejiang Hospital, Hangzhou, China.
The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
Front Oncol. 2022 Feb 24;12:816884. doi: 10.3389/fonc.2022.816884. eCollection 2022.
The pathogenesis of gastric cancer (GC) is still not fully understood. We aimed to find the potential regulatory network for ceRNA (circRNA-miRNA-immune-related mRNA) to uncover the pathological molecular mechanisms of GC. The expression profiles of circRNA, miRNA, and mRNA in gastric tissue from GC patients were downloaded from the Gene Expression Omnibus (GEO) datasets. Differentially expressed circRNAs, miRNAs, and immune-related mRNAs were filtered, followed by the construction of the ceRNA (circRNA-miRNA-immune-related mRNA) network. Functional annotation and protein-protein interaction (PPI) analysis of immune-related mRNAs in the network were performed. Expression validation of circRNAs and immune-related mRNAs was performed in the new GEO and TCGA datasets and experiment. A total of 144 differentially expressed circRNAs, 216 differentially expressed miRNAs, and 2,392 differentially expressed mRNAs were identified in GC. Some regulatory pairs of circRNA-miRNA-immune-related mRNA were obtained, including hsa_circ_0050102-hsa-miR-4537-NRAS-Tgd cells, hsa_circ_0001013-hsa-miR-485-3p-MAP2K1-Tgd cells, hsa_circ_0003763-hsa-miR-145-5p-FGF10-StromaScore, hsa_circ_0001789-hsa-miR-1269b-MET-adipocytes, hsa_circ_0040573-hsa-miR-3686-RAC1-Tgd cells, and hsa_circ_0006089-hsa-miR-5584-3p-LYN-neurons. Interestingly, FGF10, MET, NRAS, RAC1, MAP2K1, and LYN had potential diagnostic value for GC patients. In the KEGG analysis, some signaling pathways were identified, such as Rap1 and Ras signaling pathways (involved NRAS and FGF10), Fc gamma R-mediated phagocytosis and cAMP signaling pathway (involved RAC1), proteoglycans in cancer (involved MET), T-cell receptor signaling pathway (involved MAP2K1), and chemokine signaling pathway (involved LYN). The expression validation of hsa_circ_0003763, hsa_circ_0004928, hsa_circ_0040573, FGF10, MET, NRAS, RAC1, MAP2K1, and LYN was consistent with the integrated analysis. In conclusion, the identified ceRNA (circRNA-miRNA-immune-related mRNA) regulatory network may be associated with the development of GC.
胃癌（GC）的发病机制仍未完全明确。我们旨在寻找ceRNA（环状RNA-微小RNA-免疫相关信使核糖核酸）的潜在调控网络，以揭示胃癌的病理分子机制。从基因表达综合数据库（GEO）数据集中下载了GC患者胃组织中环状RNA、微小RNA和信使核糖核酸的表达谱。筛选出差异表达的环状RNA、微小RNA和免疫相关信使核糖核酸，随后构建ceRNA（环状RNA-微小RNA-免疫相关信使核糖核酸）网络。对网络中的免疫相关信使核糖核酸进行功能注释和蛋白质-蛋白质相互作用（PPI）分析。在新的GEO和TCGA数据集中以及实验中对环状RNA和免疫相关信使核糖核酸进行表达验证。在GC中总共鉴定出144个差异表达的环状RNA、216个差异表达的微小RNA和2392个差异表达的信使核糖核酸。获得了一些环状RNA-微小RNA-免疫相关信使核糖核酸的调控对，包括hsa_circ_0050102-hsa-miR-4537-NRAS-Tgd细胞、hsa_circ_0001013-hsa-miR-485-3p-MAP2K1-Tgd细胞、hsa_circ_0003763-hsa-miR-145-5p-FGF10-基质评分、hsa_circ_0001789-hsa-miR-1269b-MET-脂肪细胞、hsa_circ_0040573-hsa-miR-3686-RAC1-Tgd细胞以及hsa_circ_0006089-hsa-miR-5584-3p-LYN-神经元。有趣的是，FGF10、MET、NRAS、RAC1、MAP2K1和LYN对GC患者具有潜在诊断价值。在京都基因与基因组百科全书（KEGG）分析中，鉴定出一些信号通路，如Rap1和Ras信号通路（涉及NRAS和FGF10）、FcγR介导的吞噬作用和cAMP信号通路（涉及RAC1）、癌症中的蛋白聚糖（涉及MET）、T细胞受体信号通路（涉及MAP2K1）以及趋化因子信号通路（涉及LYN）。hsa_circ_0003763、hsa_circ_0004928、hsa_circ_0040573、FGF10、MET、NRAS、RAC1、MAP2K1和LYN的表达验证与综合分析结果一致。总之，所鉴定的ceRNA（环状RNA-微小RNA-免疫相关信使核糖核酸）调控网络可能与GC的发生发展相关。
