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Abstract：
This study aims to investigate the role of anoikis-related genes in diabetic foot (DF) by utilizing bioinformatics analysis to identify key genes associated with anoikis in DF. We selected the GEO datasets GSE7014, GSE80178 and GSE68183 for the extraction and analysis of differentially expressed anoikis-related genes (DE-ARGs). GO analysis and KEGG analysis indicated that DE-ARGs in DF were primarily enriched in apoptosis, positive regulation of MAPK cascade, anoikis, focal adhesion and the PI3K-Akt signalling pathway. Based on the LASSO and SVM-RFE algorithms, we identified six characteristic genes. ROC curve analysis revealed that these six characteristic genes had an area under the curve (AUC) greater than 0.7, indicating good diagnostic efficacy. Expression analysis in the validation set revealed downregulation of CALR in DF, consistent with the training set results. GSEA results demonstrated that CALR was mainly enriched in blood vessel morphogenesis, endothelial cell migration, ECM-receptor interaction and focal adhesion. The HPA database revealed that CALR was moderately enriched in endothelial cells, and CALR was found to interact with 63 protein-coding genes. Functional analysis with DAVID suggested that CALR and associated genes were enriched in the phagosome component. CALR shows promise as a potential marker for the development and treatment of DF.
摘要：
本研究旨在通过生物信息学分析来确定与糖尿病足（DF）相关的关键基因，以探讨与DF相关的基因。我们选择了GEO数据集GSE7014，GSE80178和GSE68183用于差异表达的失巢凋亡相关基因（DE-ARG）的提取和分析。GO和KEGG分析表明DF中DE-ARGs主要富集细胞凋亡,MAPK级联的正向调节，Anoikis,局灶性粘附和PI3K-Akt信号通路。基于LASSO和SVM-RFE算法,我们确定了六个特征基因。ROC曲线分析显示,这6个特征基因的曲线下面积(AUC)大于0.7,表明良好的诊断效能。验证组中的表达分析揭示了DF中CALR的下调，与训练集结果一致。GSEA结果表明，CALR主要富集在血管形态发生中，内皮细胞迁移，ECM-受体相互作用和粘着斑。HPA数据库显示，CALR在内皮细胞中中度富集，发现CALR与63个蛋白质编码基因相互作用。用DAVID进行的功能分析表明，CALR和相关基因富含吞噬体成分。CALR有望成为DF发展和治疗的潜在标志物。
