Cai Liang, Zhang Bingdong
Department of Anesthesiology in Cardiovascular Institute, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Dis Markers. 2023 Apr 12;2023:5493415. doi: 10.1155/2023/5493415. eCollection 2023.
Performing cardiopulmonary bypass (CPB) to reduce ischemic injury during surgery is a common approach to cardiac surgery. However, this procedure can lead to systemic inflammation and multiorgan dysfunction. Therefore, elucidating the molecular mechanisms of CPB-induced inflammatory cytokine release is essential as a critical first step in identifying new targets for therapeutic intervention. The GSE143780 dataset which is mRNA sequencing from total circulating leukocytes of the neonatorum was downloaded from the Gene Expression Omnibus (GEO) database. A total of 21 key module genes were obtained by analyzing the intersection of differentially expressed gene (DEG) and gene coexpression network analysis (WGCNA), and then, 4 genes (TRAF3IP2-AS1, PPARGC1B, CD4, and PDLIM5) were further confirmed after the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) screening and were used as hub genes for CPB-induced inflammatory cytokine release in patients with congenital heart defects. The enrichment analysis revealed 21 key module genes mainly related to the functions of developmental cell growth, regulation of monocyte differentiation, regulation of myeloid leukocyte differentiation, ERK1 and ERK2 cascade, volume-sensitive anion channel activity, and estrogen receptor binding. The result of gene set enrichment analysis (GSEA) showed that the hub genes were related to different physiological functions of cells. The ceRNA network established for hub genes includes 3 hub genes (PPARGC1B, CD4, and PDLIM5), 55 lncRNAs, and 34 miRNAs. In addition, 4 hub genes have 215 potential therapeutic agents. Finally, expression validation of the four hub genes revealed that they were all significantly low expressed in the surgical samples than before.
在心脏手术中进行体外循环（CPB）以减少缺血性损伤是心脏手术的常见方法。然而，该过程可导致全身炎症和多器官功能障碍。因此，阐明CPB诱导的炎性细胞因子释放的分子机制作为识别治疗干预新靶点的关键第一步至关重要。从基因表达综合数据库（GEO）下载了GSE143780数据集，该数据集是来自新生儿总循环白细胞的mRNA测序数据。通过分析差异表达基因（DEG）与基因共表达网络分析（WGCNA）的交集，共获得21个关键模块基因，然后，经过最小绝对收缩和选择算子（LASSO）和支持向量机递归特征消除（SVM-RFE）筛选后，进一步确认了4个基因（TRAF3IP2-AS1、PPARGC1B、CD4和PDLIM5），并将其用作先天性心脏病患者CPB诱导的炎性细胞因子释放的枢纽基因。富集分析显示，21个关键模块基因主要与发育细胞生长、单核细胞分化调节、髓系白细胞分化调节、ERK1和ERK2级联、容积敏感阴离子通道活性以及雌激素受体结合的功能相关。基因集富集分析（GSEA）结果表明，枢纽基因与细胞的不同生理功能相关。为枢纽基因建立的ceRNA网络包括3个枢纽基因（PPARGC1B、CD4和PDLIM5）、55个lncRNA和34个miRNA。此外，4个枢纽基因有215种潜在治疗药物。最后，对4个枢纽基因的表达验证显示，它们在手术样本中的表达均显著低于术前。
