AUTHOR=Yao Ziping , Zhang Bihui , Niu Guochen , Yan Ziguang , Tong Xiaoqiang , Zou Yinghua , Yang Min 

TITLE=Subunits of C1Q Are Associated With the Progression of Intermittent Claudication to Chronic Limb-Threatening Ischemia

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.864461

DOI=10.3389/fcvm.2022.864461

ISSN=2297-055X

ABSTRACT=Background: The pathophysiological mechanisms of IC progression to CLTI are still vague, and which of IC patients will become CLTI is unknown. The present study aimed to investigate the key molecules and pathways mediating IC progression to CLTI by a quantitative bioinformatic analysis of a public RNA-sequencing database of PAD patients to screen biomarkers discriminating IC and CLTI.
Methods: The GSE120642 dataset was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between IC and CLTI tissues were analysed using the "edgeR" packages of R. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to explore the functions of DEGs. Protein–protein interaction (PPI) networks were established by the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized by Cytoscape software. Hub genes were selected by plugin cytoHubba. Gene set enrichment analysis was performed, and receiver operating characteristic curves were used to evaluate the predictive values of hub genes.
Results: A total of 137 upregulated and 21 downregulated DEGs were identified. Functional enrichment clustering analysis revealed a significant association between intersecting genes and the complement and coagulation cascade pathways. The PPI network was constructed with 155 nodes and 105 interactions. The most significantly enriched pathway was complement activation. C1QB, C1QA, C1QC, C4A, and C1R were identified and validated as hub genes due to the high degree of connectivity. The area under the curve values for the five hub genes were greater than .95, indicating high accuracy for discriminating IC and CLTI.
Conclusions: The complement activation pathway is associated with IC progression to CLTI. C1QB, C1QA, C1QC, C4A, and C1R might serve as potential early biomarkers of CLTI.