Elevation of carbohydrate antigen 125 in chronic heart failure may be caused by mechanical extension of mesothelial cells from serous cavity effusion

Abstract

Objectives: The practical application of elevated carbohydrate antigen 125 (CA125) to predict clinical outcome in chronic heart failure (CHF) is under debate. The mechanism for this CA125 elevation remains unknown. We hypothesize that mechanical stress on mesothelial cells initiates CA125 synthesis.

Design and methods: A total of 191 patients suffering from edema and/or dyspnea were enrolled. 109 patients were diagnosed as CHF, and 82 patients without CHF were assigned as control group. Echocardiography, CA125, N-terminal pro-brain natriuretic peptide (NT-proBNP), and other biochemical parameters were measured. All enrolled patients underwent heart function classification.

Results: Patients with serous cavity effusion (SCE) demonstrated higher serum CA125 than patients without SCE (82.91 (61.90-103.92) vs. 44.98 (29.66-60.30) U/mL, P<0.001). In the absence of SCE, CA125 levels in CHF patients were slightly higher than non-CHF patients (52.37 (34.85-69.90) vs. 35.15 (23.81-46.49) U/mL, P=0.017). Additionally, compared with non-CHF patients, CHF patients had higher levels of high-sensitivity C-reactive protein (hsCRP) and lower superoxide dismutase (SOD). In all enrolled patients, CA125 levels were negatively correlated with SOD concentrations (r=-0.567, P<0.001), and positively correlated with hsCRP levels (r=0.608, P<0.001). Receiver operating characteristic curve analysis showed that CA125 was better in predicting SCE than NT-proBNP, while NT-proBNP was more suitable for predicting CHF than CA125. The in vitro study demonstrated that MUC16, the CA125 coding gene, was up-regulated by mechanical stretch on human mesothelial cell line (MeT-5A).

Conclusions: CA125 elevation in CHF was associated with SCE. Mechanical extension of mesothelial cells from SCE plays an important role in CA125 increase.

Keywords: A/G; AAO; ALB; AOR; AUC; CA125; CHF; Carbohydrate antigen 125; Chronic heart failure; DBP; GLB; IVSd; LA; LVDd; LVEF; LVPWd; M/F; MeT-5A; N-terminal pro-brain natriuretic peptide; NT-proBNP; NYHA; New York Heart Association classes; Oxidative stress; ROC; RT-PCR; RVDd; SBP; SCE; SOD; Serous cavity effusion; Systemic inflammation; TP; albumin; albumin/globulin ratio; aortic root; areas under the curve; ascending aorta; carbohydrate antigen 125; chronic heart failure; diastolic blood pressure; globulin; high-sensitivity C-reactive protein; hsCRP; human mesothelial cell line; interventricular septum depth; left atrium; left ventricular diastolic dimension; left ventricular ejection fraction; left ventricular posterior wall depth; male/female; receiver operator characteristic; reverse transcription polymerase chain reaction; right ventricular diastolic dimension; serous cavity effusion; superoxide dismutase; systolic blood pressure; total protein.