ArticleWorld journal of urology2026
Integrated analysis of extrachromosomal circular DNA and transcriptome reveals associations between microbial profiles and Immunoinflammatory markers in hypospadias.
Article in World journal of urology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Extrachromosomal DNA as a platform for epigenetic reprogramming in cancer.Molecular cancer · 2026Review
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14 authors.
Funding
Abstract
purposeHypospadias, a prevalent congenital anomaly characterized by abnormal urethral opening formation, poses significant psychological and physical challenges to patients. This study aimed to elucidate the function of extrachromosomal circular DNA (eccDNA) found in foreskin tissues of hypospadias patients as well as its association with immunoinflammatory responses and microbial dynamics.
methodsWe used Circle-seq to quantify eccDNA abundance and RNA sequencing for gene expression profiling. Foreskin samples were carefully collected from 54 patients with hypospadias and compared against samples from 59 control individuals with phimosis. The hypospadias cohort was significantly younger (mean 3.2 years) than controls (mean 7.5 years), which might be a major limitation that confounded immune and microbiome findings and limited causal interpretation. Tissue samples were collected after standard surgical disinfection, which may influence microbial detection.
resultsOur analysis revealed a striking increase in eccDNA abundance, identifying 2,387,050 eccDNA elements in the hypospadias cohort, contrasted with only 608,545 in the control group. Furthermore, gene expression profiling demonstrated the up-regulation of 541 genes and the down-regulation of 257 genes, with significant enrichment in pathways related to inflammatory responses and lymphocyte differentiation, indicating dysregulated immune responses in hypospadias. Complementary findings of elevated white blood cell counts and inflammatory cytokines underscored the heightened immunoinflammatory response associated with this condition. The activated immunoinflammatory response showed positive associations with eccDNA abundance and sizes. Notably, microbial profiling uncovered that Escherichia coli constituted 43.11% of the foreskin microbiome in hypospadias patients, considerably exceeding levels found in phimosis. Escherichia coli abundance was associated with increased immunoinflammatory response and higher eccDNA levels.
conclusionThis study underscores a complex association between immunoinflammatory responses and microbial communities in the pathophysiology of eccDNA dynamics in hypospadias, revealing important implications for future research and potential therapeutic strategies.
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