Analytical and clinical evaluation of ABEI-based CA125 immunoassays in heart failure: method comparison, biomarker profiles and prognostic insights

Carbohydrate antigen 125 (CA125), which is traditionally used in ovarian cancer diagnostics, is increasingly recognized as a marker of congestion and inflammation in heart failure (HF). This study compared the analytical performance of N-(4-aminobutyl)-N-ethylisoluminol (ABEI)-based CA125 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) assays on the Maglumi® X6 analyzer with that of the Roche Cobas e602 system and explored the relationship of CA125 with biomarkers of adverse remodeling in HF with reduced ejection fraction (HFrEF). Imprecision testing and method comparison were performed on matched serum samples from 108 HFrEF patients. CA125 concentrations were evaluated in relation to the New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), galectin-3, and soluble suppression of tumorigenicity 2 (sST2) levels. Prognostic value was assessed by Kaplan-Meier survival analysis using the 35 U/mL threshold. The ABEI based CA125 assay showed low imprecision [coefficient of variation (CV)≤4.5%] and strong agreement with the Cobas e602 assay ( R =0.97, slope=1.06, P <0.001). CA125 levels increased progressively with NYHA class ( P =0.02), correlated negatively with LVEF ( R =–0.38, P <0.001) and positively with galectin-3 ( R =0.21, P =0.03) and sST2 ( R =0.57, P <0.001). Elevated CA125 levels (≥35 U/mL) were associated with significantly increased cardiovascular mortality ( P <0.001). ABEI-based CA125 measurement provides an analytical performance comparable to that of Cobas e602. In HFrEF, CA125 is correlated with clinical severity, fibrosis/inflammation biomarkers, and prognosis. Its integration into multimarker strategies, particularly alongside NT-proBNP and sST2, may enhance risk stratification and therapeutic monitoring, including the response to sodium–glucose cotransporter-2 (SGLT2) inhibitor therapy.