Ma Xiaole, Cui Miao, Guo Yuntong
Department of Gastrointestinal Surgery, First Hospital of Shanxi Medical University, Taiyuan, China.
Department of Geriatrics, First Hospital of Shanxi Medical University, Taiyuan, China.
Front Genet. 2024 Jul 1;15:1385559. doi: 10.3389/fgene.2024.1385559. eCollection 2024.
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, , , , , , , , , and . and 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.
肥胖和胃癌（GC）是全球普遍存在的疾病。特别是，肥胖患者的数量每年都在增加，而GC的发病率和死亡率居高不下。因此，这些疾病严重影响了个体的生活质量。虽然有证据表明这两种疾病之间存在密切关联，但这种共病的潜在机制仍不清楚。
我们从基因表达综合数据库中获取了GSE94752和GSE54129的基因表达谱。为了研究相关的生物学过程，使用基因本体论和京都基因与基因组百科全书对肥胖和GC中共享的差异表达基因进行通路富集分析。随后基于相互作用基因检索工具（STRING）数据库建立蛋白质-蛋白质相互作用（PPI）网络，接着使用Cytoscape插件MCODE筛选该网络中的核心模块和中心基因。此外，我们仔细研究了与这些中心基因相关的转录因子（TFs）、miRNA和mRNA的共表达网络以及相互作用网络。最后，我们使用不同的数据集进行进一步分析，以验证枢纽基因的重要性。
共选择了246个共享的差异表达基因（209个上调和37个下调）用于后续分析。功能分析强调了炎症和免疫相关通路在这两种疾病中的关键作用。使用Cytoscape插件CytoHubba，鉴定出9个枢纽基因，即 、 、 、 、 、 、 、 和 。通过使用不同数据集进行验证， 和 被确认为最终的枢纽基因。TF-miRNA-mRNA调控网络表明，与枢纽基因主要相关的TFs包括RELA和NFKB1，而主要相关的miRNAs包括has-miR-195-5p和has-miR-106a-5p。
使用生物信息学方法，我们从基因表达综合数据集中鉴定出肥胖和GC的两个枢纽基因。此外，我们构建了枢纽基因、TFs和miRNAs的网络，并鉴定出主要相关的TFs和miRNAs。这些因素可能参与了肥胖和GC的共同分子机制。
