Unveiling Urinary Biomarkers, Crucial Genes, and Immune Infiltration in Lupus Nephritis Patients

Abstract

Abstract Background This study was conducted to investigate the expression patterns and biological roles of urinary long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in individuals diagnosed with lupus nephritis (LN). Methods The study cohort comprised six participants: three with systemic lupus erythematosus (SLE) involving LN, three with SLE without LN, and three healthy controls (CON). Microarray technology was employed to analyze urinary mRNAs and lncRNAs, thereby exploring alterations in overall RNA expression. Functional insights into dysregulated differentially expressed mRNAs (DEMs) associated with LN were derived through gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). Furthermore, the construction of a protein-protein interaction (PPI) network was accomplished using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). The identification of immune-related cell types was facilitated by Single-sample Gene Set Enrichment Analysis (ssGSEA). To predict potential drug candidates based on differentially expressed genes (DEGs), Connectivity Map (CMap) analysis was conducted. Results Within the urine samples of SLE patients, a total of 247 mRNAs and 602 lncRNAs exhibited differential expression relative to the control group. Among these, 83 down-regulated and 141 up-regulated DEMs were specifically discerned in patients with LN. GO analysis of the network highlighted enrichment in processes such as transcriptional regulation, intrinsic apoptotic signaling pathways in response to DNA damage, and the regulation of mitophagy. KEGG pathway analysis primarily revealed enrichment in protein processing within the endoplasmic reticulum, apoptosis, and the P53 signaling pathway. Co-expression and PPI network analysis suggested that nodes with higher degrees of connectivity were concentrated in pathways related to apoptosis and autophagy. An assessment of immune infiltration unveiled a correlation between activated B cells and CD56dim natural killer (NK) cells with LN pathogenesis. The prediction of drugs implicated inhibition of mechanistic Aurora kinase A (AURKA) as a primary targeted intervention. The molecular docking process confirmed the robust binding activity of hub genes' components. Conclusion This study has illuminated the distinct expression profiles of urinary long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in lupus nephritis (LN) patients. These profiles, particularly in the context of apoptosis, autophagy, and immune cell involvement, provide valuable insights into LN's underlying mechanisms. The identification of potential therapeutic targets, such as mechanistic AURKA, offers promising directions for future interventions in LN management.