Yerukala Sathipati Srinivasulu, Carter Tonia, Soodi Deepa, Somto Nwaedozie, Shukla Sanjay K, Petronovich John, Ingrid Glurich, Braxton John, Sharma Param
Center for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield, WI, 54449, USA.
Department of Cardiology, Marshfield Clinic Health System, Marshfield, WI, 54449, USA.
Sci Rep. 2025 May 28;15(1):18658. doi: 10.1038/s41598-025-03042-3.
Early detection of atrial fibrillation (AFib) is crucial for altering its natural progression and complication profile. Traditional demographic and lifestyle factors often fail as predictors of AFib. This study investigated pre-operative, circulating microRNAs (miRNAs) as potential biomarkers for post-operative AFib (POAF) in patients undergoing coronary artery bypass grafting (CABG). We used an array polymerase chain reaction method to detect pre-operative, circulating miRNAs in seven patients who subsequently developed POAF after CABG (cases) and eight patients who did not develop POAF after CABG (controls). The top 10 miRNAs from 84 candidates were selected and assessed for their performance in predicting POAF using machine learning models, including Random Forest, K-Nearest Neighbors (KNN), XGBoost, and Support Vector Machine (SVM). The Random Forest and XGBoost models showed superior predictive performance, with test area under the curve (AUC) values of 0.76 and 0.83, respectively. Differential expression analysis revealed four upregulated miRNAs-hsa-miR-96-5p, hsa-miR-184, hsa-miR-17-3p, and hsa-miR-200-3p-that overlapped with the POAF-miRNA signature. The POAF-miRNA signature was significantly associated with various cardiovascular diseases, including acute myocardial infarction, hypertrophic cardiomyopathy, and heart failure. Biological pathway analysis indicated these miRNAs target key signaling pathways involved in cardiovascular pathology, such as the MAPK, PI3K-Akt, and TGF-beta signaling pathways. The identified miRNAs demonstrate significant potential as predictive biomarkers for AFib post-CABG, implicating critical cardiovascular pathways and highlighting their role in POAF development and progression. These findings suggest that miRNA signatures could enhance predictive accuracy for POAF, offering a novel, noninvasive approach to early detection and personalized management of this condition.
早期检测心房颤动(AFib)对于改变其自然病程和并发症情况至关重要。传统的人口统计学和生活方式因素往往无法作为AFib的预测指标。本研究调查了冠状动脉旁路移植术(CABG)患者术前循环微RNA(miRNA)作为术后心房颤动(POAF)潜在生物标志物的情况。我们采用阵列聚合酶链反应方法检测了7例CABG术后发生POAF的患者(病例组)和8例CABG术后未发生POAF的患者(对照组)术前的循环miRNA。从84个候选miRNA中选出排名前10的miRNA,并使用机器学习模型(包括随机森林、K近邻算法(KNN)、极端梯度提升(XGBoost)和支持向量机(SVM))评估它们预测POAF的性能。随机森林和XGBoost模型显示出卓越的预测性能,测试曲线下面积(AUC)值分别为0.76和0.83。差异表达分析揭示了4种上调的miRNA——hsa-miR-96-5p、hsa-miR-184、hsa-miR-17-3p和hsa-miR-200-3p——它们与POAF-miRNA特征重叠。POAF-miRNA特征与多种心血管疾病显著相关,包括急性心肌梗死、肥厚型心肌病和心力衰竭。生物学通路分析表明,这些miRNA靶向参与心血管病理过程的关键信号通路,如丝裂原活化蛋白激酶(MAPK)、磷脂酰肌醇-3激酶-蛋白激酶B(PI3K-Akt)和转化生长因子-β(TGF-β)信号通路。所鉴定的miRNA显示出作为CABG术后AFib预测生物标志物的巨大潜力,涉及关键的心血管通路,并突出了它们在POAF发生和发展中的作用。这些发现表明,miRNA特征可以提高POAF的预测准确性,为这种疾病的早期检测和个性化管理提供一种新的非侵入性方法。