Hsa_circRNA_101015 and hsa_circRNA_104310 as novel biomarkers of childhood steroid-resistant nephrotic syndrome

Abstract

Background: Nephrotic syndrome (NS) is the leading cause of glomerular diseases in pediatric patients, among whom corticosteroid responsiveness has been shown to be closely associated with prognosis. Circular RNAs (circRNAs) play crucial roles in various pathophysiological processes and hold significant promise as biomarkers. This study investigated circRNAs for their ability to discriminate patients with steroid-resistant nephrotic syndrome (SRNS) from steroid-sensitive nephrotic syndrome (SSNS), and to explore the pathogenesis underlying NS.

Methods: Microarray analysis was performed to detect circRNA profiles. Total RNA was purified from peripheral blood mononuclear cells obtained from three children, each with SRNS and SSNS. The seven identified candidate circRNAs were validated among 31 SRNS and 30 SSNS patients utilizing real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The clinical diagnostic value of the circRNAs was assessed by the receiver operating characteristic curve. Bioinformatic analysis was further performed to understand the intricate biological functions of circRNAs.

Results: Overall, 209 downregulated and 65 upregulated differentially expressed circRNAs were identified in patients with SRNS vs. SSNS. Validation by qRT-PCR revealed that the expression levels of hsa_circRNA_101015 and hsa_circRNA_104310 were considerably lower in the SRNS than the SSNS group. These two circRNAs had area under the curve values of 0.90 and 0.84, respectively, which validated their diagnostic power to discriminate SRNS from SSNS. Further, bioinformatic analysis revealed enrichment of the Wnt signaling pathway.

Conclusion: Hsa_circRNA_101015 and hsa_circRNA_104310 are novel predictive biomarkers for distinguishing SRNS from SSNS, and may participate in the pathogenesis of NS.

Keywords: Child; Circular RNA; Nephrotic syndrome; Wnt signaling pathway.