Comprehensive analysis of single-cell and bulk transcriptome unravels immune landscape of atherosclerosis and develops a S100 family based-diagnostic model

The S100 family of calcium-binding proteins (S100s) had been tightly related to the biological processes of various cardiovascular diseases. This study aims to investigate the expression of S100s in Atherosclerosis (AS) and explore their potential as diagnostic biomarkers and therapeutic targets.

We analyzed multiple sequencing datasets from the GEO database to compare the expression profiles of S100s in AS tissues versus normal samples. Employing unsupervised clustering techniques, AS subtypes were discerned based on the intricate variations in S100-related gene expression profiles. Subsequent analyses delved into immune cell infiltration and GSVA pathway enrichment, shedding light on the nuanced immune landscape characterizing diverse AS subtypes. Machine learning techniques were employed to develop a diagnostic model for AS. Single-cell RNA analysis was utilized to investigate the cellular distribution of S100 hub genes in AS.

Unsupervised clustering analysis identified two distinct AS subtypes (C1 and C2), characterized by specific S100 gene expression patterns. The RF-based diagnostic model exhibited the highest efficacy (AUC=0.881), and the top five genes (S100A4, S100A10, S100A11, S100A13, S100Z) were used to construct a diagnostic nomogram.

This study systematically elucidates the roles of S100s in AS, offering insights into molecular subtyping, immune characteristics, and diagnostic model construction. The findings provide valuable implications for the precise treatment and prognosis assessment of AS and pave the way for further research into related mechanisms.