Evaluation of LCN2 and miR-8078 as diagnostic biomarkers for congenital heart disease-associated pulmonary arterial hypertension.

This study aimed to evaluate the diagnostic value of lipocalin 2 (LCN2) and microRNA-8078 (miR-8078) in congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH). Seventy-six patients were diagnosed with CHD-PAH according to established clinical guidelines (including mean pulmonary arterial pressure (mPAP), pulmonary artery wedge pressure, and pulmonary vascular resistance) via right heart catheterization. Based on their mPAP, they were stratified into non-PAH (mPAP < 25 mm Hg; n = 28), mild PAH (25 ≤ mPAP < 35 mm Hg; n = 21), and moderate-to-severe PAH (mPAP ≥ 35 mm Hg; n = 27) groups. Plasma LCN2 levels and miR-8078 expression were quantified using Enzyme-linked immunosorbent assay and RT-qPCR, respectively. The diagnostic value was analysed using receiver operating characteristic curves. Correlation analysis assessed associations between biomarkers and hemodynamic parameters. Multi-variate logistic regression identified independent predictors of CHD-PAH. Plasma LCN2 (135.1 [40.2] vs 67.7 [17.7] ng/ml; P < .05) and relative miR-8078 expression (4.2 ± 1.1 vs 2.3 ± 1.3 fold; P < .05) were significantly elevated in the moderate-to-severe PAH group compared with the non-PAH group. Both markers showed positive correlations with mPAP (LCN2: r = 0.691, P < .001; miR-8078: r = 0.481, P < .001) and pulmonary artery systolic pressure (LCN2: r = 0.579, P < .001; miR-8078: r = 0.391, P < .001). Notably, LCN2 levels positively correlated with miR-8078 expression (r = 0.407, P < .001). For diagnosing moderate-to-severe PAH, the area under the curve (AUC) was 0.883 for LCN2 and 0.749 for miR-8078. The combined model yielded a numerically higher AUC of 0.896, but did not significantly differ from LCN2 alone. Univariate regression analysis identified both LCN2 and miR-8078 as significant predictors of CHD-PAH. LCN2 was identified as an independent risk factor for CHD-PAH. Plasma LCN2 and miR-8078 are significantly elevated in patients with CHD-PAH and correlate positively with hemodynamic severity. LCN2, in particular, serves as a robust independent biomarker for the diagnosis and severity assessment of CHD-PAH. Consequently, LCN2 and miR-8078 hold promise as potential non-invasive biomarkers for the diagnosis and severity assessment of CHD-PAH.