Abstract
Venous thromboembolism (VTE) is a common vascular disease and a major cause of mortality. Development of early diagnostic biomarkers that accurately predict the occurrence of VTE is key for its initial management. The present study was designed to identify potential early diagnostic biomarkers based on the crosstalk between pyroptosis and VTE. The GSE19151 and GSE48000 datasets were utilized as the training and validation cohorts, respectively. Pyroptosis-related genes (PRGs) were sourced from the existing literature. Multiple bioinformatic analyses were conducted to pinpoint key PRGs in VTE. The possible functions of these genes were elucidated through gene set enrichment analysis (GSEA). Molecular regulatory networks were synthesized to probe into the underlying molecular mechanism of VTE. Moreover, a total of 5 pairs of frozen blood samples were analyzed quantifiably by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to evaluate the expression levels of these biomarkers. a total of Five critical biomarkers (RPL31, RPL34, RPL9, RPS27L and HINT1) were eventually screened, with significantly elevated expression levels observed in VTE samples in both the training and validation cohorts compared with control. The RT-qPCR results further confirmed that expression trends of these genes were consistent with those in the GSE19151 and GSE48000 datasets. GSEA indicated a correlation between the five biomarkers and ribosomal proteins as well as oxidative phosphorylation signaling pathways, suggesting their potential role in triggering VTE by regulating pyroptosis-inflammation-coagulation axis. A total of five critical pyroptosis-related biomarkers have been initially characterized, showing potential for early diagnosis of VTE. While these findings are promising, further investigation into the precise mechanisms and clinical thresholds is warranted.