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Identification and Clinical Validation of the Role of Anoikis-Related Genes in Diabetic Foot

INTERNATIONAL WOUND JOURNAL(2024)

Shandong Univ

Cited 0|Views17
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.
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Key words
anoikis,bioinformatics analysis,CALR,diabetic foot,endothelial cell
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要点】:本研究通过生物信息学方法识别与糖尿病足(DF)相关的失巢凋亡基因,并验证其临床作用,发现CALR基因可能作为DF发展和治疗的潜在生物标志物。

方法】:使用LASSO和SVM-RFE算法筛选特征基因,并利用GEO数据集进行差异表达失巢凋亡基因(DE-ARGs)的提取和分析。

实验】:选取GSE7014、GSE80178和GSE68183三个GEO数据集进行实验,通过ROC曲线分析验证特征基因的诊断效能,并在验证集中分析CALR基因表达情况,使用GSEA和HPA数据库进行功能验证,结果显示CALR在糖尿病足中具有显著作用。