Bioinformatics Identification and Validation of Pyroptosis-Related Diagnostic Biomarkers in Diabetic Nephropathy

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Abstract

Background: Diabetic nephropathy (DN) is a common and serious issue in nephrology. This disease often develops without clear early symptoms. Its causes are complex and multiple. Good markers for early diagnosis are still lacking. Pyroptosis is a form of programmed cell death. It triggers strong inflammatory responses. Emerging evidences indicate that pyroptosis may be involved in the development and progression of DN. Methods: In this study, we found genes that are shared by DN and pyroptosis. We then studied key genes in more detail and tested them by using weighted gene co-expression network analysis, machine learning methods, single-cell RNA sequencing, and molecular docking to check their predictive value and reliability. Results: We identified two key genes, MYH9 and CDC20 . Both genes were highly expressed in podocytes. Functional analysis showed that MYH9 is mainly related to the immune infiltration of naive B cells and resting mast cells. CDC20 is related to the immune infiltration of resting mast cells and naive CD4 T cells. Molecular docking and competing endogenous RNA (ceRNA) analysis also supported the diagnostic and predictive value of MYH9 and CDC20 in DN. Conclusion : MYH9 and CDC20 serve as potential predictive biomarkers elucidating the role of pyroptosis in DN pathogenesis, and may offer promising avenues for early diagnosis and intervention in DN.

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