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Bioinformatics and experimental studies of atherosclerosis-related endothelial dysfunction genes in renal calculi and

Aina Li1, Chenjing Liu2, Xiangshen Liu2

  • 1Department of Cardiology, the First Affiliated Hospital of Fujian Medical University, FuZhou, China.

Plos One
|August 4, 2026
PubMed

Insights

This study identifies key genes, UCHL1 and NEK2, linked to kidney stones (KS) and atherosclerosis (AS) by analyzing gene expression. These findings offer insights into the molecular mechanisms of KS and potential therapeutic targets.

Area of Science:

  • Biomedical Science
  • Molecular Biology
  • Genetics

Background:

  • Patients with kidney stones (KS) exhibit an elevated risk of atherosclerosis (AS).
  • Endothelial dysfunction (ED) is a known contributor to AS, but its specific role in KS pathogenesis is not well understood.
  • Investigating AS-related ED genes in KS is crucial for understanding disease mechanisms.

Purpose of the Study:

  • To identify and characterize the roles and regulatory mechanisms of AS-related endothelial dysfunction genes in kidney stone disease.
  • To discover potential biomarkers for KS associated with AS.
  • To explore therapeutic strategies targeting identified molecular pathways.

Main Methods:

  • Analysis of three public gene expression datasets (GSE73680, GSE117518, GSE132651).
  • Differential gene expression analysis, LASSO regression for biomarker selection, and RT-qPCR validation.
  • Bioinformatic analyses including GeneMANIA, GSEA, pathway analysis, ceRNA network construction, and drug prediction.

Main Results:

  • Identified 22 differentially expressed genes (DEGs) associated with both KS and AS.
  • Selected UCHL1 and NEK2 as key biomarkers through LASSO regression and validation.
  • Uncovered biomarker involvement in cell adhesion, focal adhesion, and lysosome pathways; NEK2 was found to be overexpressed in KS samples.
  • Predicted 17 potential drugs targeting NEK2, including pazopanib and palbociclib.

Conclusions:

  • UCHL1 and NEK2 are validated key biomarkers linking kidney stones and atherosclerosis.
  • Comprehensive molecular and regulatory network analyses provide insights into KS pathogenesis.
  • Findings support future personalized treatment strategies and drug development for kidney stone disease.