Increasing evidence suggested nephrolithiasis has a close linkage with carotid atherosclerosis (CAS), with Randall's plaque (RP) being a precursor to kidney stones. Our study aimed to examine the crosstalk genes and potential molecular mechanisms between RP and CAS. We obtained microarray data for RP and CAS from the Gene Expression Omnibus (GEO) and used weighted gene co-expression network analysis (WGCNA) and differential gene expression (DEG) analysis to identify shared genes. By integrating WGCNA and DEG analysis, Asporin (ASPN) was identified as the key gene connecting RP and CAS, with its diagnostic potential assessed via a receiver operating characteristic (ROC) curve. Immune infiltration studies showed a significant correlation between ASPN and various immune cells in RP and CAS. ASPN was found to be less expressed in RP and CAS tissues compared to normal tissues, as confirmed by immunohistochemistry (IHC) and quantitative reverse-transcription PCR (qRT-PCR). The rat model confirmed the human tissue findings. ASPN can elucidate the shared pathogenic mechanisms underlying the two conditions, including immune response and osteoblast differentiation.
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