Koroner Kalp Hastalığında Melatoninin Rolünün Ortaya Çıkarılması: Yeni Biyobelirteçlerin Tanımlanması ve Deneysel Doğrulanması

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Abstract Melatonin (ME) affects multiple systems in coronary heart disease (CHD), including lipid/glucose metabolism, blood pressure, and sleep-wake regulation, while also promoting coronary thrombosis through unknown mechanisms. This study uses bioinformatics to identify ME-related biomarkers for CHD diagnosis and treatment. The GSE179789 and GSE113079 datasets were obtained from a public database. Biomarkers were selected via differential analysis and expression validation. Gene set enrichment analysis (GSEA) was performed, and regulatory as well as drug‑biomarker networks were constructed. Biomarker expression was further validated in clinical samples using RT‑qPCR. MAP2K2 and PGD were identified as reliable CHD biomarkers, showing significant up‑regulation in CHD samples across both datasets. GSEA indicated their involvement in multiple pathways, including ribosome, prion diseases, and Parkinson's disease. Complex regulatory interactions were observed among lncRNAs, miRNAs, and biomarkers; for instance, four lncRNAs (NEAT1, AP000766.1, LINC02381, XIST) regulated PGD via hsa‑let‑7e‑5p. Additionally, 29 transcription factors (e.g., STAT1, BRD3, HDAC1, CBFB) co‑regulated both biomarkers. Finally, 41 drugs (e.g., cobimetinib fumarate, selumetinib sulfate) were predicted to target MAP2K2, while three (penicillamine, pralmorelin, phenobarbital) targeted PGD. In summary, MAP2K2 and PGD serve as CHD biomarkers, offering new insights into disease pathogenesis.

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