BACKGROUND/AIM: The incidence of cancer continues to rise, highlighting the urgent need for reliable, non-invasive biomarkers to support early diagnosis and improve treatment outcomes. In addition to circulating microRNAs, circulating PIWI-interacting RNAs (cir-piRNAs) have emerged as promising candidates. Although the biological functions of piRNAs are not yet fully understood, they are known to suppress transposable elements and may regulate structural genes involved in tumorigenesis. In this two-phase study, we aimed to identify serum piRNAs with diagnostic potential for clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: A total of 238 serum samples from ccRCC patients and 208 healthy controls were analyzed. In the exploratory phase, next-generation sequencing (NGS) was performed on pooled samples representing different clinical stages of ccRCC and healthy controls. RESULTS: We identified 35 piRNAs with significantly different expression (p<0.01) between groups. Based on statistical significance, read abundance, and fold change, six piRNAs were selected for the training phase and subsequently, three piRNAs, piR-24672, piR-27140, and piR-28876, were selected for validation. Validation by RT-qPCR in an independent cohort confirmed significantly reduced levels of all three piRNAs in ccRCC patients. ROC analysis demonstrated that piR-28876 is a superior diagnostic biomarker, reaching AUC=0.787, with 85.0% specificity and 66.3% sensitivity in distinguishing ccRCC patients from healthy controls. CONCLUSION: Circulating piRNAs, particularly piR-24672, piR-27140, and piR-28876, may serve as potential non-invasive biomarkers for the early detection of ccRCC.

Central European Institute of Technology Masaryk University Brno Czech Republic

Central European Institute of Technology Masaryk University Brno Czech Republic;

Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic

Department of Urologic Oncology Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Urology University Hospital Brno Faculty of Medicine Masaryk University Brno Czech Republic

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