PMID- 35433866
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2297-055X (Print)
IS  - 2297-055X (Electronic)
IS  - 2297-055X (Linking)
VI  - 9
DP  - 2022
TI  - Subunits of C1Q Are Associated With the Progression of Intermittent Claudication 
      to Chronic Limb-Threatening Ischemia.
PG  - 864461
LID - 10.3389/fcvm.2022.864461 [doi]
LID - 864461
AB  - BACKGROUND: The pathophysiological mechanisms of intermittent claudication (IC) 
      progression to chronic limb-threatening ischemia (CLTI) are still vague and which 
      of patients with IC will become CLTI are unknown. This 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 patients with 
      peripheral artery disease (PAD) 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 analyzed using the "edgeR" packages of R. The Gene Ontology and the 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 the 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 DEGs 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 0.95, 
      indicating high accuracy for discriminating IC and CLTI. CONCLUSION: 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.
CI  - Copyright (c) 2022 Yao, Zhang, Niu, Yan, Tong, Zou and Yang.
FAU - Yao, Ziping
AU  - Yao Z
AD  - Department of Interventional Radiology and Vascular Surgery, Peking University 
      First Hospital, Beijing, China.
FAU - Zhang, Bihui
AU  - Zhang B
AD  - Department of Interventional Radiology and Vascular Surgery, Peking University 
      First Hospital, Beijing, China.
FAU - Niu, Guochen
AU  - Niu G
AD  - Department of Interventional Radiology and Vascular Surgery, Peking University 
      First Hospital, Beijing, China.
FAU - Yan, Ziguang
AU  - Yan Z
AD  - Department of Interventional Radiology and Vascular Surgery, Peking University 
      First Hospital, Beijing, China.
FAU - Tong, Xiaoqiang
AU  - Tong X
AD  - Department of Interventional Radiology and Vascular Surgery, Peking University 
      First Hospital, Beijing, China.
FAU - Zou, Yinghua
AU  - Zou Y
AD  - Department of Interventional Radiology and Vascular Surgery, Peking University 
      First Hospital, Beijing, China.
FAU - Yang, Min
AU  - Yang M
AD  - Department of Interventional Radiology and Vascular Surgery, Peking University 
      First Hospital, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20220401
PL  - Switzerland
TA  - Front Cardiovasc Med
JT  - Frontiers in cardiovascular medicine
JID - 101653388
PMC - PMC9010542
OTO - NOTNLM
OT  - Bioinformatics
OT  - chronic limb-threatening ischemia
OT  - complement
OT  - intermittent claudication
OT  - mechanism
OT  - peripheral artery disease
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/19 06:00
MHDA- 2022/04/19 06:01
PMCR- 2022/01/01
CRDT- 2022/04/18 06:39
PHST- 2022/01/28 00:00 [received]
PHST- 2022/03/07 00:00 [accepted]
PHST- 2022/04/18 06:39 [entrez]
PHST- 2022/04/19 06:00 [pubmed]
PHST- 2022/04/19 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fcvm.2022.864461 [doi]
PST - epublish
SO  - Front Cardiovasc Med. 2022 Apr 1;9:864461. doi: 10.3389/fcvm.2022.864461. 
      eCollection 2022.