Identification of Biomarker in Kidney Stone Disease by Integrating Transcriptomics and Olink Proteomics: A Case–Control Study

Background
Kidney stone disease (KSD) is a prevalent disorder characterized by considerable morbidity and growing healthcare burden. However, the pathogenesis of kidney stone formation remains incompletely understood. This study aimed to explore the gene expression profiles and underlying mechanisms associated with calcium oxalate (CaOx) stone formation, as well as to identify potential urinary biomarkers for CaOx KSD.

Methods
Blood and urine samples were collected from patients diagnosed with KSD and matched healthy controls (HCs). A comprehensive transcriptomic profile of peripheral blood mononuclear cells (PBMCs) was developed utilizing RNA sequencing (RNA-seq). Additionally, the expression levels of 92 inflammation-related proteins in the urine were detected using Olink proteomics.

Results
A total of 1,063 differentially expressed genes (DEGs) were identified between the KSD and HC groups. Gene ontology (GO) and gene set enrichment analysis (GSEA) revealed that production of molecular mediator of immune response, inflammatory response, and oxidative stress were dysregulated in the KSD group. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the most DEGs were enriched in extracellular matrix (ECM)-receptor interaction. Eight inflammation-related proteins exhibited significant alterations in the KSD group. Notably, the level of matrix metalloproteinase-1 (MMP-1) demonstrated the greatest fold change and highest mean decrease accuracy in the urine of the KSD group.

Conclusion
Our preliminary findings suggest the molecular mechanisms and functional pathways that might be involved in CaOx kidney stone formation and identify MMP-1 as a potential urinary biomarker associated with CaOx KSD.