Identification of Parthanatos-related biomarkers in hemorrhagic shock and study of potential molecular mechanisms

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Abstract Hemorrhagic shock (HS) remains a critical condition, yet the involvement of parthanatos is not well defined. This study aimed to identify parthanatos-related biomarkers in HS and elucidate their mechanisms. By analyzing HS datasets and parthanatos-related genes (PARGs), candidate genes were screened via differential expression and key modular analysis. Biomarkers were selected using machine learning, receiver operating characteristic (ROC) curves, and expression validation. Nomograms were constructed and evaluated. Functional mechanisms of biomarkers were explored through chromosomal localization, subcellular localization, enrichment analysis, immune infiltration, and regulatory networks. Expression of biomarkers was validated with reverse transcription quantitative polymerase chain reaction (RT-qPCR). Glycogenin-1 (GYG1) and Protein Phosphatase 1 Regulatory Subunit 3D (PPP1R3D) were identified as parthanatos-related biomarkers in HS. Nomograms showed strong predictive potential for HS. Enrichment analysis revealed co-enrichment in oxidative phosphorylation, Parkinson’s disease, and proteasome pathways. Both biomarkers were correlated with various immune cells, and hsa-mir-181d-5p and hsa-mir-25-3p were identified as co-targeting GYG1 and PPP1R3D. Drug analysis revealed Digoxin as a potential therapeutic agent. RT-qPCR confirmed upregulation of GYG1 and PPP1R3D in HS samples. GYG1 and PPP1R3D were identified as biomarkers associated with parthanatos in HS, providing a reference for early diagnosis of HS and optimization of treatment options.

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