作者
Wei Zhang,Ying Huang,Duo Zheng,Qianqian Chen,Rong Huang,Yue Wang,Xiaofei Li
摘要
This study aims to analyze the plasma levels of miR-8078 in patients with congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) and explore its diagnostic value and potential mechanisms in CHD-PAH. Plasma samples were collected from 110 patients with congenital heart disease. Based on the mean pulmonary artery pressure (PAPm) measured by right heart catheterization, the patients were divided into three groups: no PAH group (Group W, PAPm < 25mmHg), mild group (Group M, 25mmHg ≤ PAPm < 35mmHg), moderate to severe group (Group H, PAPm ≥ 35mmHg), and a control group (Group C) consisting of 40 healthy individuals. The expression levels of miR-8078 were detected using reverse transcription-polymerase chain reaction (RT-PCR). The target genes and their biological functions regulated by miR-8078 were predicted using software such as Targetscan, PicTar, and miRDB. Statistical analysis was performed to evaluate the correlation between miR-8078 and hemodynamic parameters in CHD-PAH, as well as its diagnostic value. The expression levels of plasma miR-8078 were significantly higher in the moderate to severe group compared to the control group, no PAH group, and mild group (p<0.05). The mild group and no PAH group showed significantly higher expression levels of miR-8078 compared to the control group (p<0.05), which was consistent with high-throughput sequencing results. KEGG pathway analysis of miR-8078 target genes revealed its association with morphine addiction, ubiquitin-mediated proteolysis, parathyroid synthesis, and secretion. GO enrichment analysis indicated its involvement in the regulation of RNA polymerase II transcription, positive regulation of MAPK signaling, ion transport across membranes, chromatin organization, and atrioventricular valve morphogenesis. Correlation analysis showed that miR-8078 expression levels were positively correlated with pulmonary artery systolic pressure, mean pulmonary artery pressure, and pulmonary vascular resistance (correlation coefficients were 0.404, 0.397, and 0.283, respectively, p<0.05). Univariate and multivariate regression analysis revealed that plasma miR-8078 (OR 1.475, 95% CI: 1.053-2.065, p<0.05) was an independent risk factor for CHD-PAH. The receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for miR-8078 alone and B-type natriuretic peptide (BNP) alone in diagnosing CHD-PAH were 0.686 and 0.851, respectively, and the AUC for combined diagnosis was 0.874, which was higher than that of individual diagnosis (p<0.05). This study suggests that miR-8078 is upregulated in CHD-PAH and its bioinformatics analysis indicates its involvement in the pathogenesis of CHD-PAH, making it a potential therapeutic target or biomarker.