Uncovering Shared Diagnostic Genes and Mechanisms in Chronic Kidney Disease and Atherosclerosis: A Bioinformatics...

The purpose of this study was to screen for common diagnostic genes and identify possible molecular mechanisms underlying CKD combined with AS using bioinformatic methods.

We retrieved the gene expression profiles of CKD and AS from the Gene Expression Omnibus (GEO). Using differential expression combined with WGCNA, we identified hub genes shared by CKD and AS. GO and KEGG enrichment analyses were conducted. To screen the diagnostic biomarker, we constructed PPI networks and applied three ML methods: least absolute shrinkage and selection operator (ASSO), random forest (RF), and Support Vector Machine-Recursive Feature Elimination (SVM-RFE). The diagnostic performance for the candidate gene was assessed by a receiver operating characteristic curve (ROC) on the training set and the external validation dataset. CIBERSORT is used to evaluate immune cell infiltration the DGIdb database predicts possible drugs for treatment.

We found a total of 119 common genes highly correlated between CKD and AS. The enrichment results showed that these genes are mainly related to the cytoskeleton in the muscle cell, vascular smooth muscle contraction, cGMP-PKG signaling pathway and NF-kappa B signaling pathway. By the integrative PPI and ML analysis, TAGLN was selected as the hub common gene. TAGLN had good diagnostic efficiency (AUC > 0.70) across the training and validation cohorts. Immune infiltration analysis showed significant dysregulation of several immune cells for both diseases. Moreover, two candidate drugs acting on TAGLN were found.

In this research, we have revealed that TAGLN was an effective diagnostic indicator in CKD-AS comorbidity. The multi-algorithms confirmed TAGLN's outstanding diagnostic ability among six independent samples. Mechanistically, cytoskeletal dysregulation seems to be the key connection of the two diseases, and there is a strong correlation between TAGLN expression and immune cell infiltration. Recombinant transforming growth factor-β1 and azacitidine could possibly function by modulating TAGLN. Our study not only reveals the molecular basis of CKD-AS comorbidity but also provides some useful targets for developing novel diagnostic or therapeutic strategies.

We believe our results provide clues to the possibility of using TAGLN as an ideal common diagnostic marker for CKD and AS, and point out some common molecular mechanisms and possible treatment targets between the two diseases that will provide new clues to future research on their pathogenesis, diagnosis, and therapy.