{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T07:27:58Z","timestamp":1767338878666,"version":"3.40.5"},"reference-count":67,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T00:00:00Z","timestamp":1706227200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,1,26]]},"abstract":"<jats:p>Pyroptosis plays a key role in the death of cells including cardiomyocytes, and it is associated with a variety of cardiovascular diseases. However, the role of pyroptosis-related genes (PRGs) in hypertrophic cardiomyopathy (HCM) is not well characterized. This study aimed to identify key biomarkers and explore the molecular mechanisms underlying the functions of the PRGs in HCM. The differentially expressed genes were identified by GEO2R, and the differentially expressed pyroptosis-related genes (DEPRGs) of HCM were identified by combining with PRGs. Enrichment analysis was performed using the \u201cclusterProfiler\u201d package of the R software. Protein-protein interactions (PPI) network analysis was performed using the STRING database, and hub genes were screened using cytoHubba. TF-miRNA coregulatory networks and protein-chemical interactions were analyzed using NetworkAnalyst. RT-PCR\/WB was used for expression validation of HCM diagnostic markers. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western Blot (WB) were used to measure and compare the expression of the identified genes in the cardiac hypertrophy model and the control group. A total of 20 DEPRGs were identified, which primarily showed enrichment for the positive regulation of cytokine production, regulation of response to biotic stimulus, tumor necrosis factor production, and other biological processes. These processes primarily involved pathways related to Renin-angiotensin system, Adipocytokine signaling pathway and NF-kappa B signaling pathway. Then, a PPI network was constructed, and 8 hub genes were identified. After verification analysis, the finally identified HCM-related diagnostic markers were upregulated gene protein tyrosine phosphatase non-receptor type 11 (<jats:italic toggle=\"yes\">PTPN11<\/jats:italic>), downregulated genes interleukin-1 receptor-associated kinase 3 (<jats:italic toggle=\"yes\">IRAK3)<\/jats:italic>, and annexin A2 (<jats:italic toggle=\"yes\">ANXA2<\/jats:italic>). Further GSEA analysis revealed these 3 biomarkers primarily related to cardiac muscle contraction, hypertrophic cardiomyopathy, fatty acid degradation and ECM\u2005\u2212\u2005receptor interaction. Moreover, we also elucidated the interaction network of these biomarkers with the miRNA network and known compounds, respectively. RT-PCR\/WB results indicated that <jats:italic toggle=\"yes\">PTPN11<\/jats:italic> expression was significantly increased, and <jats:italic toggle=\"yes\">IRAK3<\/jats:italic> and <jats:italic toggle=\"yes\">ANXA2<\/jats:italic> expressions were significantly decreased in HCM. This study identified <jats:italic toggle=\"yes\">PTPN11, IRAK3<\/jats:italic>, and <jats:italic toggle=\"yes\">ANXA2<\/jats:italic> as pyroptosis-associated biomarkers of HCM, with the potential to reveal the development and pathogenesis of HCM and could be potential therapeutic targets.<\/jats:p>","DOI":"10.1097\/md.0000000000036799","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T03:03:45Z","timestamp":1706756625000},"page":"e36799","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":6,"title":["Identification and validation of pyroptosis-related genes as potential biomarkers for hypertrophic cardiomyopathy: A comprehensive bioinformatics analysis"],"prefix":"10.1097","volume":"103","author":[{"given":"Xin","family":"Tang","sequence":"first","affiliation":[{"name":"School of Public Health, Guizhou Medical University, Guiyang, 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