hsa_circ_0134625对冠心病的预测价值及潜在调控机制研究

Predictive value and potential regulatory mechanisms of hsa_circ_0134625 in coronary artery disease

目的探索hsa_circ_0134625对冠心病的预测价值及潜在调控机制。方法基于高通量测序结果筛选冠心病患者血浆中差异表达的环状RNA(circRNA)。回顾性选取2022年7月至2023年12月在宁波大学第一附属医院行冠脉造影检查的患者161例(包括冠心病组81例和对照组80例),采集血液并检测比较两组对象hsa_circ_0134625表达水平,采用logistic回归分析冠心病与临床特征的关系;采用logistic回归、极限梯度提升树、高斯朴素贝叶斯方法构建冠心病预测模型,采用ROC曲线评估模型性能,基于沙普利加和解释(SHAP)对最优模型进行事后分析。基于生物信息学方法和公共基因表达综合数据库构建circRNA-微小RNA(miRNA)-信使RNA调控网络并进行功能富集分析,推测hsa_circ_0134625在冠心病发病过程中的潜在调控机制。结果冠心病组hsa_circ_0134625表达水平明显高于对照组[1.44(1.02,1.76)比1.02(0.66,1.60),P=0.010]。hsa_circ_0134625是冠心病的独立预测因子(OR=1.720,95%CI:1.145~2.584,P=0.009)。基于hsa_circ_0134625预测冠心病的AUC为0.629(0.540~0.718);而基于hsa_circ_0134625联合临床数据构建的预测模型中,以极限梯度提升树算法的预测模型综合性能最佳,分类准确度、AUC分别为0.730、0.818。SHAP分析显示该模型中hsa_circ_0134625对冠心病的预测具有重要影响。生物信息学分析显示hsa_circ_0134625与hsa-miR-515-5p、hsa-miR-646、hsa-miR-639表达有关;通路富集分析显示,主要与磷脂酰肌醇-3激酶/蛋白激酶B、叉头框转录因子和血管内皮生长因子信号通路有关。结论hsa_circ_0134625在冠心病患者血浆中呈高表达,有望成为预测冠心病的生物学标志物;调控网络揭示了hsa_circ_0134625在冠心病的发生、发展中的潜在调控机制。

Objective To explore the predictive value and potential regulatory mechanisms of hsa_circ_0134625 in coronary artery disease.Methods Differentially expressed circular RNA(circRNA)in the plasma of coronary artery disease patients were screened based on high-throughput sequencing results.A retrospective selection of 161 patients who underwent coronary angiography at the First Affiliated Hospital of Ningbo University from July 2022 to December 2023 was conducted(including 81 cases in the coronary artery disease group and 80 in the control group).Blood samples were collected,and the expression levels of hsa_circ_0134625 were compared between the two groups.Logistic regression was conducted to analyze the relationship between coronary artery disease and clinical characteristics.The prediction models for coronary artery disease were constructed using logistic regression,extreme gradient boosting(XGBoost),and Gaussian Naive Bayes methods.The model performance was evaluated by ROC curves,and post-hoc analysis on the optimal model was performed using Shapley additive explanation(SHAP).Based on bioinformatics methods and public gene expression databases,a circRNA-miRNA-mRNA regulatory network was constructed,and functional enrichment analysis was performed to infer the potential regulatory mechanisms of hsa_circ_0134625 in the pathogenesis of coronary artery disease.Results The expression level of hsa_circ_0134625 was significantly higher in the coronary artery disease group compared to the control group[1.44(1.02,1.76)vs.1.02(0.66,1.60),P=0.010].hsa_circ_0134625 is an independent predictor for coronary artery disease(OR=1.720,95%CI:1.145-2.584,P=0.009).The AUC for predicting coronary artery disease based on hsa_circ_0134625 was 0.629(0.540-0.718);in the predictive models combining hsa_circ_0134625 with clinical data,the model using the XGBoost algorithm showed the best overall performance,with a classification accuracy and AUC of 0.730 and 0.818,respectively.SHAP analysis indicated that hsa_circ_0134625 had a significant impact on coronary artery disease prediction within XGBoost model.Bioinformatics analysis showed that hsa_circ_0134625 was associated with the expressions of hsa-miR-515-5p,hsa-miR-646,and hsa-miR-639;pathway enrichment analysis revealed that the main focus was on the phosphatidylinositol-3-kinase/protein kinase B,forkhead box O,and vascular endothelial growth factor signaling pathways.Conclusion hsa_circ_0134625 is highly expressed in the plasma of coronary artery disease and shows potentials as a biomarker for predicting coronary artery disease;the regulatory network reveals the potential regulatory mechanisms of hsa_circ_0134625 in the occurrence and progression of coronary artery disease.