BK polyomavirus-associated nephropathy (BKPyVAN) is a serious complication of kidney transplantation. Numerous kidney diseases such as BKPyVAN have been shown to cause mitochondrial dysfunction. This study aims to identify key mitochondria-related genes in BKPyVAN. We merged two datasets, GSE72925 and GSE47199, to form a training set after batch-effect removal. Hub mitochondria-related genes in BKPyVAN were identified using bioinformatics tools. The functional information of the hub genes was analyzed using gene set enrichment analysis (GSEA). A mouse model of polyomavirus (MPyV) infection was established to verify the expression levels of B-cell lymphoma 2-related protein A1 (BCL2A1), Caspase-3 (CASP3), and threonine synthase like 1 (THNSL1) in BKPyVAN. We identified nine mitochondria-related genes that were differentially expressed between BKPyVAN and stable graft samples and correlated with BKPyVAN onset. Among these, three genes (THNSL1, BCL2A1, and CASP3) were identified as robust mitochondria-related genes in BKPyVAN. THNSL1 and BCL2A1 were upregulated and CASP3 was downregulated in BKPyVAN samples. Moreover, THNSL1 and BCL2A1 were upregulated and CASP3 was downregulated in MPyV kidney tissue samples. These genes showed a significant diagnostic value for BKPyVAN. GSEA revealed the potential involvement of these genes in the immune pathways. Additionally, we found correlations between these genes and immune cell infiltration in BKPyVAN patients. Our study identified three robust biomarkers (THNSL1, BCL2A1 and CASP3) for BKPyVAN that might be potential targets for diagnosis and treatment. These biomarkers may be involved in immune pathways and show a significant correlation with immune cell infiltration, suggesting their critical role in BKPyVAN pathogenesis.

The authors have declared no competing interest.

This study was supported by the Science and Technology Project Program of the Liaoning Province (2022020774-JH2/1015).

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Data supporting the conclusions of this study are openly available in the Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/) database, with the following IDs: GSE72925, GSE47199, GSE120495, and GSE75693.