Characterization and comparative profiling of piRNAs in serum biopsies of pediatric Wilms tumor patients.
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Piwi-interacting RNAs (piRNAs) are small non-coding RNAs involved in transposon silencing and linked to cancer progression. However, their role in Wilms tumors (WT) remains unexplored. We conducted a thorough analysis and characterization of piRNAs in serum liquid biopsies of WT patients. Our study examined their expression patterns and functional annotations related to WT pathogenesis, as well as their clinical potential for diagnosis and monitoring. We identified 307 piRNAs expressed in WT serum samples, with 4% classified as repeat-related and 96% as non-repeat-related. The most abundant repeat-related piRNAs originated from LINEs retrotransposon, while tRNA-derived piRNAs were the most prevalent among non-repeat-related piRNAs. Furthermore, a distinct profile of 34 piRNAs showed significant differential expression in WT patients compared to healthy controls-22 downregulated and 12 upregulated. The target genes of differentially expressed piRNAs exhibited significant enrichment in biological pathways related to cytokine activity, inflammatory responses, TGF-beta signaling, p38 MAPK, and ErbB signaling. These genes are also involved in DNA damage response, DNA methylation, cell cycle regulation, as well as kidney development and function. Low expression levels of several piRNAs, especially piR-hsa-1,913,711, piR-hsa-28,190, piR-hsa-28,849, piR-hsa-28,848, and piR-hsa-28,318, showed significant diagnostic potential as non-invasive biomarkers for WT (AUC > 0.8, p < 0.05). Their expression levels also significantly correlated with adverse pathological features, including metastasis, anaplasia, and bilateral WT development. In conclusion, non-transposon-related piRNAs may serve as reliable biomarkers for WT and possess potential non-germline functions, particularly in regulating DNA methylation, cell growth, immune responses, and immune responses. Further studies are warranted to elucidate their functional significance.