Transcriptomic analysis of differential expression and correlation of coding and non-coding RNAs in urine from patients with idiopathic membranous nephropathy
摘要
The incidence rate of idiopathic membranous nephropathy (IMN) has been increasing, and its pathogenesis is still unclear. Exploring new diagnostic molecular markers and the molecular mechanisms of IMN.
MethodsFifteen healthy controls and fifteen IMN patients were recruited. Clinical baseline data of all participants, including age, gender, and body mass index (BMI), along with histopathological staging (Ehrenreich-Churg classification) and immunohistochemical staining results for phospholipase A2 receptor (PLA2R), were collected and analyzed. Meanwhile, peripheral blood and urine samples were obtained to detect renal function-related biochemical indicators, including serum creatinine (Scr), estimated glomerular filtration rate (eGFR), serum albumin, 24-hour urinary protein (24 h UPT), serum total cholesterol (TC), anti-PLA2R antibody titer, and serum immunoglobulin G (IgG). Urine samples (n = 10) were also used for high-throughput sequencing analysis.
ResultsSerum albumin was significantly downregulated in the IMN group, while 24 h UPT, TC, anti-PLA2R Ab titer, and IgG were upregulated. MicroRNA (miRNA) transcriptomic analysis identified 34 differentially expressed (DE) miRNAs. Hsa-miR-576-3p, hsa-miR-766-5p, and NovelmiRNA-837 exhibited strong diagnostic potential via ROC curve analysis (AUC > 0.8). Sixty-four DE mRNAs were identified in IMN tissues, with enrichment in pathways such as Ribosome and MAPK signaling-fly. ENST00000481739 (RXRA) was upregulated in IMN, correlated with anti-PLA2R Ab titer, and exhibited diagnostic potential (AUC = 0.929). Thirty-five DE lncRNAs were identified in IMN, enriched in autophagy, mitophagy, and apoptosis pathways. TCONS_00180924, TCONS_00176280, TCONS_00208611 correlated significantly with TC, 24-h urinary protein, and anti-PLA2R Ab titer.
ConclusionsThis study provides a foundation for developing non-invasive diagnostic tools and targeted therapies for IMN.