Uncovering Candidate mRNAs, Signaling Pathways and Immune Cells in Atherosclerotic Plaque and Ischemic Stroke

Abstract

Background

The specific molecular mechanistic link between atherosclerotic plaques and ischemic stroke (IS) is not clear. The aim of this study is to explore the potential molecular relationship between atherosclerotic plaques and IS.

Methods

All data were downloaded from the Gene Expression Omnibus (GEO) database. Key hub differentially expressed mRNAs (DEmRNAs) related to atherosclerotic plaques and IS were identified by differential expression analysis and least absolute shrinkage and selection operator (LASSO) analysis. Subsequently, a diagnostic model was established based on the expression of key hub DEmRNAs and logistic regression. In order to understand the molecular mechanism of key hub DEmRNAs, the transcription factor (TF) regulatory network and mRNA-miRNA-lncRNA regulatory network were also constructed. In addition, functional enrichment analysis and single-sample Gene Set Enrichment Analysis (ssGSEA) analysis were also performed.

Results

Four key hub DEmRNAs (ADCY3, CLDN7, PPM1B and RRAS2) were identified by differential expression analysis and LASSO analysis. Moreover, the diagnostic model based on four key hub DEmRNAs has excellent diagnostic accuracy. We also found that Type 1 T helper cell may be associated with IS caused by atherosclerosis based on ssGSEA analysis. In the mRNA-miRNA-lncRNA regulatory network, we found that multiple signaling axes such as RRAS2-hsa-miR-3150b-3p-ILF3-AS1, PPM1B-hsa-miR-541-5p-LINC00294, CLDN7-hsa-miR-184-LINC00467 and ADCY3-hsa-miR-488-3p-URB1-AS1 may play an important role in the progression of IS. In addition, some signaling pathways, including chemokine signaling pathway, MAPK signaling pathway and cAMP signaling pathway, may be involved in regulating IS.

Conclusion

The identified key molecules, signaling pathways and immune cells may help to provide a theoretical basis for exploring the relationship between atherosclerotic plaque and the progression of IS.

Keywords:

• ischemic stroke
• atherosclerotic plaques
• diagnostic accuracy
• Type 1 T helper cell
• functional enrichment
• mRNA-miRNA-lncRNA regulatory network

Data Sharing Statement

All data in this study were downloaded from GEO database. The persistent accessible web links for GEO is https://www.ncbi.nlm.nih.gov/geo/. Accession numbers of datasets used in the study are GSE207252, GSE146882, GSE28829 and GSE16561 in GEO. All data generated or analyzed during this study are included in this published article.

Ethics Approval and Consent to Participate

The present study was approved by the Ethics Committee of The Second Affiliated Hospital of Shandong First Medical University. This study complied with the Declaration of Helsinki. Written informed consent was obtained from all participants.

Disclosure

Xianjing Zhang and Tingting Han can be considered as co-first authors. The authors declare that they have no conflicts of interest.

Additional information

Funding

There is no funding to report.