Identification of key molecular markers of acute coronary syndrome using peripheral blood transcriptome sequencing analysis and mRNA-lncRNA co-expression network construction

ABSTRACT

Acute coronary syndrome (ACS) is a term used to describe major cardiovascular diseases, and treatment of in-stent restenosis in patients with ACS remains a major clinical challenge. Further investigation into molecular markers of ACS may aid early diagnosis, and the treatment of ACS and post-treatment recurrence. In the present study, total RNA was extracted from the peripheral blood samples of 3 patients with ACS, 3 patients with percutaneous coronary intervention (PCI)_non-restenosis, 3 patients with PCI_restenosis and 3 healthy controls. Subsequently, RNA library construction and high-throughput sequencing were performed. DESeq2 package in R was used to screen genes that were differentially expressed between the different samples. Moreover, the intersection of the differentially expressed mRNAs (DEmRNAs) and differentially expressed long noncoding RNAs (DElncRNAs) obtained. GeneCodis4.0 was used to perform function enrichment for DEmRNAs, and lncRNA-mRNA co-expression network was constructed. The GSE60993 dataset was utilized for diagnostic analysis, and the aforementioned investigations were verified using in vitro studies. Results of the present study revealed a large number of DEmRNAs and DElncRNAs in the different groups. We selected genes in the top 10 of differential expression and also involved in the co-expression of lncRNA-mRNA for diagnostic analysis in the GSE60993 dataset. The area under curve (AUC) of PDZK1IP1 (0.747), PROK2 (0.769) and LAMP3 (0.725) were all >0.7. These results indicated that the identified mRNAs and lncRNAs may act as potential clinical biomarkers, and more specifically, PDZK1IP1, PROK2 and LAMP3 may act as potential biomarkers for the diagnosis of ACS.

KEYWORDS:

• Acute coronary syndrome
• mRNA
• long non-coding RNA
• differential expression
• diagnostic

Disclosure statement

The authors declare that they have no competing interests.

Consent for publication

All authors have agreed to the publication of the work.

Ethics approval and consent to participate

All experimental procedures were approved by The Third Hospital of Hebei Medical University (K2019-012-1). The written consent was obtained from the all patients. All participants were informed as to the purpose of this study, and that this study complied with the Declaration of Helsinki.

Highlights

• Transcriptome sequencing analysis provides potential biomarkers for the diagnosis and treatment of ACS.

• PDZK1IP1, PROK2 and LAMP3 may act as the potential diagnostic genetic biomarkers in ACS.

• Identification of potential key genes provides direction for further research.

Availability of data and materials

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. The transcriptome data have been uploaded to Gene Expression Omnibus (accession no. GSE179645).

Authors’ contributions

All authors have made important contributions to data analysis, drafting the article or revising the article.

Additional information

Funding

Hebei Province Key Research and Development Program Project (192777112D).