Risk prediction model of IgA nephropathy constructed by glycosylation genes and analysis of immune cell infiltration
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1.Department of Nephrology,the Affiliated Nanjing Hospital of Nanjing Medical University(Nanjing First Hospital), Nanjing 210006 ;2.Department of Nephrology,the Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100 ,China

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R692.3

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    Abstract:

    Objective:This study aimed to exploration of glycosylation-related genes and immune infiltration analysis of IgA nephropathy(IgAN). Methods:IgAN datasets were obtained from the GEO database. Then differentially expressed glycosylation-related genes and functional enrichment analyses were identified. Next,optimal feature genes(OFGs)were selected using least absolute shrinkage and selection operator(LASSO),support vector machine recursive feature elimination(SVM-RFE),and random forest algorithms. The expression of OFGs in IgAN were validated by immunohistochemistry staining,Western blot,and the Nephroseq v5 database. OFGs were further used to create a nomogram model,compare immune cell infiltration and construct a ceRNA network. Results:After screening,three OFGs of ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1(ST8SIA1),chondroitin sulfate synthase 1(CHSY1)and phosphatidylinositol N-acetylglucosaminyl transferase subunit H(PIGH)were first reported. The nomogram model showed that OFGs had good predictive value for IgAN occurrence. Compared to normal samples,IgAN showed increased infiltration of CD8+ T cells,naive CD4+ T cell,memory activated CD4+ T cells,resting dendritic cells,and resting mast cells,while naive B cells,plasma cells,memory resting CD4+ T,activated mast cells,and neutrophils were reduced. OFGs were associated with memory activated CD4+ T cells,memory resting CD4+ T cells,naive CD4+ T cell,naive B cells,etc. The validation experiments also revealed that the expression levels of CHSY1 and PIGH were significantly decreased,while the expression level of ST8SIA1 was significantly increased in IgAN compared with minimal change nephropathy. Of note,the expression levels of OFGs in diabetic nephropathy and minimal change nephropathy were not statistically different. A ceRNA network consisting of 117 lncRNAs,67 miRNAs,and 3 OFGs was constructed. Conclusion:ST8SIA1,CHSY1,and PIGH were identified as potential targets for diagnosis and treatment of IgAN. In conjunction with immune cell infiltration and ceRNA network,these results offer a novel perspective for future research on IgAN.

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CHEN Mengxing, ZONG Huimin, ZHANG Yang. Risk prediction model of IgA nephropathy constructed by glycosylation genes and analysis of immune cell infiltration[J].,2024,(12):1671-1681.

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  • Received:March 21,2024
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  • Online: December 16,2024
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