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基于生物信息学分析鉴定和验证糖尿病足中的铁死亡相关基因。

Identification and verification of ferroptosis-related genes in diabetic foot using bioinformatics analysis.

机构信息

The First Clinical Medical College, Guangdong Medical University, Zhanjiang, China.

Medical school, Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming, China.

出版信息

Int Wound J. 2023 Oct;20(8):3191-3203. doi: 10.1111/iwj.14198. Epub 2023 May 30.

Abstract

Ferroptosis is a novel form of cell death that plays a key role in several diseases, including inflammation and tumours; however, the role of ferroptosis-related genes in diabetic foot remains unclear. Herein, diabetic foot-related genes were downloaded from the Gene Expression Omnibus and the ferroptosis database (FerrDb). The least absolute shrinkage and selection operator regression algorithm was used to construct a related risk model, and differentially expressed genes were analysed through immune infiltration. Finally, we identified relevant core genes through a protein-protein interaction network, subsequently verified using immunohistochemistry. Comprehensive analysis showed 198 genes that were differentially expressed during ferroptosis. Based on functional enrichment analysis, these genes were primarily involved in cell response, chemical stimulation, and autophagy. Using the CIBERSORT algorithm, we calculated the immune infiltration of 22 different types of immune cells in diabetic foot and normal tissues. The protein-protein interaction network identified the hub gene TP53, and according to immunohistochemistry, the expression of TP53 was high in diabetic foot tissues but low in normal tissues. Accordingly, we identified the ferroptosis-related gene TP53 in the diabetic foot, which may play a key role in the pathogenesis of diabetic foot and could be used as a potential biomarker.

摘要

铁死亡是一种新的细胞死亡形式,在包括炎症和肿瘤在内的几种疾病中发挥关键作用;然而,铁死亡相关基因在糖尿病足中的作用尚不清楚。在此,从基因表达综合数据库(GEO)和铁死亡数据库(FerrDb)中下载了与糖尿病足相关的基因。使用最小绝对收缩和选择算子回归算法构建了相关风险模型,并通过免疫浸润分析差异表达基因。最后,我们通过蛋白质-蛋白质相互作用网络鉴定了相关的核心基因,并通过免疫组织化学进行了验证。综合分析显示,在铁死亡过程中有 198 个基因表达差异。基于功能富集分析,这些基因主要参与细胞反应、化学刺激和自噬。使用 CIBERSORT 算法,我们计算了糖尿病足和正常组织中 22 种不同类型免疫细胞的免疫浸润。蛋白质-蛋白质相互作用网络确定了枢纽基因 TP53,根据免疫组织化学,TP53 在糖尿病足组织中的表达较高,而在正常组织中表达较低。因此,我们在糖尿病足中鉴定到了铁死亡相关基因 TP53,其可能在糖尿病足的发病机制中起关键作用,并可作为潜在的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79e0/10502281/c0f6a4766822/IWJ-20-3191-g003.jpg

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