<p>Gene expression profiling reveals candidate biomarkers and probable molecular mechanism in diabetic peripheral neuropathy</p>

Abstract

Purpose To investigate the molecular mechanism and search for candidate biomarkers in the gene expression profile of patients with diabetic peripheral neuropathy (DPN). Methods Differentially expressed genes (DEGs) of progressive vs non-progressive DPN patients in dataset GSE24290 were screened. Functional enrichment analysis was conducted, and hub genes were extracted from the protein–protein interaction network. The expression level of hub genes in serum samples in another dataset GSE95849 was obtained, followed by the ROC curve analysis. Results A total of 352 DEGs were obtained from dataset GSE24290. They were involved in 14 gene ontology terms and 10 Kyoto Encyclopedia of Genes and Genomes pathways, mainly related to lipid metabolism. Eight hub genes (LEP, APOE, ADIPOQ, FABP4, CD36, GPAM, CIDEC, and PNPLA4) were revealed, and their expression level was obtained in dataset GSE95849. The receiver operating characteristic curve analysis indicated that CIDEC (AUC=1), APOE (AUC=0.833), CD36 (AUC=0.803), and PNPLA4 (AUC=0.861) might be candidate serum biomarkers of DPN. Conclusion Lipid metabolism of Schwann cells might be inhibited in progressive DPN. CIDEC, APOE, CD36, and PNPLA4 might be potential predictive biomarkers in the early DPN diagnosis of patients with DM.

The Multifunctionality of CD36 in Diabetes Mellitus and Its Complications—Update in Pathogenesis, Treatment and Monitoring

“…Many types of cells express CD36: platelets [ 37 ], erythrocytes [ 50 ], monocytes and macrophages [ 51 ], microvascular endothelial cells [ 52 ], adipocytes [ 53 ], skeletal and cardiac muscle cells [ 54 ], islets of Langerhans [ 12 ], kidney cells [ 55 ], retina cells [ 20 ], and peripheral nerve cells [ 21 ]. There is also a circulating form of CD36 called soluble CD36 (sCD36).…”

“…Among the diabetic complications we have described, the role of CD36 in the pathogenesis of DPN is the least well established. Gene expression profile studies in DPN identified several candidates associated with the lipid metabolism and inflammation potentially involved in the initiation and progression of this complication; among them is CD36 [ 21 , 247 ]. Increased CD36 expression in peripheral nerves was observed in BKS db / db mice [ 246 ] and individuals [ 27 ] with DPN.…”

“…Conditions such as hyperglycemia and dyslipidemia significantly change CD36 expression, its function, and its signaling pathways. The CD36-dependent mechanisms are important events in the pathogenesis of diabetic complications, such as nephropathy [ 14 , 15 , 16 , 17 ], retinopathy [ 18 , 19 , 20 ], neuropathy [ 21 , 22 ], and cardiomyopathy [ 23 , 24 , 25 , 26 ]. Importantly, CD36 disrupts the functions of organs in a tissue-specific manner by several different mechanisms.…”

<p>Identification of Hub Genes in Type 2 Diabetes Mellitus Using Bioinformatics Analysis</p>

“…Zhou et al identified the potential predictive biomarkers of diabetic peripheral neuropathy (DPN) from two GEO datasets by functional enrichment analysis, PPI network, and Receiver-Operator Characteristic (ROC) curve analysis. 22 Li et al analyzed three mRNA microarray datasets using bioinformatics analysis methods, and sixteen hub genes were identified as potential diagnostic biomarkers for hepatocellular carcinoma (HCC). 23 Xiong et al used the gene expression profiles from GEO datasets to identify the molecular mechanisms and the key hub genes that may contribute to synovial inflammation in patients with rheumatoid arthritis.…”

The Protective Effect and Mechanism of Dexmedetomidine on Diabetic Peripheral Neuropathy in Rats

“…Indeed, the simultaneous production of superoxide and nitric oxide contributes to the production of peroxynitrite, which can rapidly cause the nitrification or nitrite of proteins for various cell types, lipid peroxidation, DNA damage, and cell apoptosis, and produce direct toxic effects on nerve tissues leading to neuropathy ( Tang et al., 2019 ; Zhou and Zhang, 2019 ). In addition, apoptosis induced by caspase-3 activation due to oxidative stress plays an important role in the progression of diabetic neuropathy ( Kamboj et al., 2010 ).…”