Unveiling the Role of Melatonin in Coronary Heart Disease: Identification and Experimental Validation of Novel Biomarkers

This bioinformatics study investigated the role of melatonin-related genes in coronary heart disease (CHD) by analyzing two publicly available gene expression datasets (GSE179789 and GSE113079). Using differential expression analysis and validation, the researchers identified two genes—MAP2K2 (a mitogen-activated protein kinase kinase) and PGD (phosphogluconate dehydrogenase)—as candidate CHD biomarkers, both showing significant upregulation in CHD samples across both datasets. Gene set enrichment analysis (GSEA) linked these genes to pathways including ribosome function, prion diseases, and Parkinson's disease. The study also mapped complex regulatory networks involving lncRNAs, miRNAs, and transcription factors; notably, four lncRNAs (NEAT1, AP000766.1, LINC02381, and XIST) were found to regulate PGD via hsa-let-7e-5p, and 29 transcription factors co-regulated both biomarkers. Drug-target network analysis predicted 41 drugs targeting MAP2K2 and 3 targeting PGD. Biomarker expression was further validated in clinical samples via RT-qPCR. Limitations include the observational and computational nature of the study, reliance on public datasets, small clinical validation cohorts typical of such designs, and the absence of functional or mechanistic experiments confirming causal roles. The study is reported as a preprint and has not undergone formal peer review.

Why this grade: While RT-qPCR validation was performed in clinical samples, the study is primarily bioinformatics-driven, observational, lacks experimental mechanistic validation, and is an unreviewed preprint, limiting the strength of human evidence for the identified biomarkers.