Identification of hub genes in the crosstalk between type 2 diabetic nephropathy and obesity according to bioinformatics analysis

Diabetic nephropathy (DN) and obesity bring a huge burden to society. Obesity plays a crucial role in the progression of type 2 DN, but the pathophysiology remains unclear. Thus, we aimed the explore the association between type 2 DN and obesity using bioinformatics method. The gene expression profiles of type 2 DN (GSE96804) and obesity (GSE94752) were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were screened with the thresholds defined as |log2FC| ≥1 and P<0.05. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Subsequently, a protein-protein interaction network was constructed based on the STRING database. Hub genes were identified, and the co-expression network was constructed. Finally, the hub genes were verified in clinical samples of 24 patients by immunohistochemistry. A total of 17 common DEGs were identified. Finally, two overlapping hub genes were identified (CCL18, C1QC). C1QC has been verified in clinical specimens. Using bioinformatics methods, the present study analyzed the common DEGs and the potential pathogenic mechanisms involved in type 2 DN and obesity. C1QC was the hub gene. Further studies are needed to clarify the specific relationships among C1QC, type 2 DN and obesity.

糖尿病肾病（Diabetic nephropathy, DN）与肥胖给社会带来沉重负担。肥胖在2型糖尿病肾病的进展中发挥关键作用，但其具体病理生理机制仍未明确。因此本研究旨在通过生物信息学方法，探讨2型糖尿病肾病与肥胖之间的关联。从基因表达综合数据库（Gene Expression Omnibus, GEO）下载2型糖尿病肾病数据集GSE96804与肥胖数据集GSE94752的基因表达谱。以|log2FC|≥1且P<0.05为筛选阈值，筛选差异表达基因（differentially expressed genes, DEGs）。开展基因本体（Gene Ontology, GO）与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析。随后基于STRING数据库构建蛋白质相互作用网络，筛选得到核心基因（Hub genes）并构建共表达网络。最后通过免疫组化实验，在24例患者的临床样本中对核心基因进行验证。本研究共鉴定出17个共同差异表达基因，最终确定2个重叠核心基因：CCL18与C1QC，其中C1QC已在临床标本中得到验证。本研究通过生物信息学方法，分析了2型糖尿病肾病与肥胖共有的差异表达基因及其潜在致病机制，其中C1QC为核心基因。未来仍需开展进一步研究，以明确C1QC、2型糖尿病肾病与肥胖三者间的具体关联。