Identification and validation of disulfidptosis-related gene signatures and their subtype in diabetic nephropathy.

Abstract

Background: Diabetic nephropathy (DN) is the most common complication of diabetes, and its pathogenesis is complex involving a variety of programmed cell death, inflammatory responses, and autophagy mechanisms. Disulfidptosis is a newly discovered mechanism of cell death. There are little studies about the role of disulfidptosis on DN. Methods: First, we obtained the data required for this study from the GeneCards database, the Nephroseq v5 database, and the GEO database. Through differential analysis, we obtained differential disulfidptosis-related genes. At the same time, through WGCNA analysis, we obtained key module genes in DN patients. The obtained intersecting genes were further screened by Lasso as well as SVM-RFE. By intersecting the results of the two, we ended up with a key gene for diabetic nephropathy. The diagnostic performance and expression of key genes were verified by the GSE30528, GSE30529, GSE96804, and Nephroseq v5 datasets. Using clinical information from the Nephroseq v5 database, we investigated the correlation between the expression of key genes and estimated glomerular filtration rate (eGFR) and serum creatinine content. Next, we constructed a nomogram and analyzed the immune microenvironment of patients with DN. The identification of subtypes facilitates individualized treatment of patients with DN. Results: We obtained 91 differential disulfidptosis-related genes. Through WGCNA analysis, we obtained 39 key module genes in DN patients. Taking the intersection of the two, we preliminarily screened 20 genes characteristic of DN. Through correlation analysis, we found that these 20 genes are positively correlated with each other. Further screening by Lasso and SVM-RFE algorithms and intersecting the results of the two, we identified CXCL6, CD48, C1QB, and COL6A3 as key genes in DN. Clinical correlation analysis found that the expression levels of key genes were closely related to eGFR. Immune cell infiltration is higher in samples from patients with DN than in normal samples. Conclusion: We identified and validated 4 DN key genes from disulfidptosis-related genes that CXCL6, CD48, C1QB, and COL6A3 may be key genes that promote the onset of DN and are closely related to the eGFR and immune cell infiltrated in the kidney tissue.