肥胖和胃癌（GC）是世界范围内的流行疾病。尤其是肥胖患者数量逐年增加，GC的发病率和死亡率也居高不下。因此，这些条件严重影响个人的生活质量。虽然证据表明这两种情况之间存在很强的关联，但这种合并症的潜在机制仍不清楚。我们从基因表达综合数据库中获得了 GSE94752 和 GSE54129 的基因表达谱。为了研究相关的生物学过程，利用基因本体论和京都基因和基因组百科全书对肥胖和GC中共有的差异表达基因进行了通路富集分析。随后基于相互作用基因搜索工具（STRING）数据库建立了蛋白质-蛋白质相互作用（PPI）网络，并使用Cytoscape插件MCODE筛选该网络中的核心模块和中心基因。此外，我们仔细检查了与这些中心基因相关的转录因子 (TF)、miRNA 和 mRNA 的共表达网络和相互作用网络。最后，我们使用不同的数据集进行了进一步的分析，以验证中心基因的显着性。总共选择了246个共有的差异表达基因（209个上调基因和37个下调基因）进行后续分析。功能分析强调了炎症和免疫相关途径在这两种疾病中的关键作用。使用Cytoscape插件CytoHubba，鉴定出9个中心基因，即CXCR4、CXCL8、CXCL10、IL6、TNF、CCL4、CXCL2、CD4和CCL2。通过使用不同数据集的验证，确认IL6和CCL4为最终的枢纽基因。 TF-miRNA-mRNA调控网络显示，主要与hub基因相关的TF包括RELA和NFKB1，而主要相关的miRNA包括has-miR-195-5p和has-miR-106a-5p。利用生物信息学方法，我们从基因表达综合数据集中确定了肥胖和 GC 的两个中心基因。此外，我们构建了中心基因、TF 和 miRNA 的网络，并确定了主要相关的 TF 和 miRNA。这些因素可能涉及肥胖和GC的常见分子机制。版权所有©2024 Ma、Cui和Guo。

Obesity and gastric cancer (GC) are prevalent diseases worldwide. In particular, the number of patients with obesity is increasing annually, while the incidence and mortality rates of GC are ranked high. Consequently, these conditions seriously affect the quality of life of individuals. While evidence suggests a strong association between these two conditions, the underlying mechanisms of this comorbidity remain unclear.We obtained the gene expression profiles of GSE94752 and GSE54129 from the Gene Expression Omnibus database. To investigate the associated biological processes, pathway enrichment analyses were conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes for the shared differentially expressed genes in obesity and GC. A protein-protein interaction (PPI) network was subsequently established based on the Search Tool for the Retrieval of Interacting Genes (STRING) database, followed by the screening of the core modules and central genes in this network using Cytoscape plug-in MCODE. Furthermore, we scrutinized the co-expression network and the interplay network of transcription factors (TFs), miRNAs, and mRNAs linked to these central genes. Finally, we conducted further analyses using different datasets to validate the significance of the hub genes.A total of 246 shared differentially expressed genes (209 upregulated and 37 downregulated) were selected for ensuing analyses. Functional analysis emphasized the pivotal role of inflammation and immune-associated pathways in these two diseases. Using the Cytoscape plug-in CytoHubba, nine hub genes were identified, namely, CXCR4, CXCL8, CXCL10, IL6, TNF, CCL4, CXCL2, CD4, and CCL2. IL6 and CCL4 were confirmed as the final hub genes through validation using different datasets. The TF-miRNA-mRNA regulatory network showed that the TFs primarily associated with the hub genes included RELA and NFKB1, while the predominantly associated miRNAs included has-miR-195-5p and has-miR-106a-5p.Using bioinformatics methods, we identified two hub genes from the Gene Expression Omnibus datasets for obesity and GC. In addition, we constructed a network of hub genes, TFs, and miRNAs, and identified the major related TFs and miRNAs. These factors may be involved in the common molecular mechanisms of obesity and GC.Copyright © 2024 Ma, Cui and Guo.