OC 42.5 - Serum proteome profiling reveals Heparanase as a candidate biomarker for chronic thromboembolic pulmonary hypertension

Monday, June 24, 2024

15:45 – 16:00 ICT

Room: Ballroom B2

Presenting Author(s)

Haobo Li

PhD student
China-Japan Friendship Hospital
Beijing, Beijing, China (People's Republic)

Co-Author(s)

YZ

Yunxia Zhang

attending physician
China-Japan Friendship Hospital
Beijing, Beijing, China (People's Republic)
MZ

Meng Zhang

attending physician
Beijing Anzhen Hospital
Beijing, Beijing, China (People's Republic)
HY

Hongwei Yang

fellow
First Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing, China (People's Republic)
SM

Shuangshuang Ma

fellow
China-Japan Friendship Hospital
Beijing, Beijing, China (People's Republic)
Linfeng Xi, MD

resident physician
China-Japan Friendship Hospital
Beijing, Beijing, China (People's Republic)
PY

Peiran Yang

professor
Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences
Beijing, Beijing, China (People's Republic)
Zhenguo Zhai, MD,PhD

professor
China-Japan Friendship Hospital, Beijing, China; National Clinical Research Center for Respiratory Diseases, Beijing, China
Beijing, Beijing, China (People's Republic)

Background: Chronic thromboembolic pulmonary hypertension (CTEPH), a long-term complication of venous thromboembolism, is characterized by the combination of large vessel obstruction and small vessel disease leading to elevated pulmonary artery pressure and increased workload on the right ventricle, ultimately resulting in right heart failure. Determining novel biomarkers for early identification of CTEPH could improve patient outcomes.

Aims: We launched a two-stage study on the plasma proteome features to identify novel CTEPH-specific biomarkers.

Methods: We used the isobaric tag for relative and absolute quantitation (iTRAQ) approach to compare the protein profiles between the serum of CTEPH patients and the healthy controls. Bioinformatics analyses and ELISA validation were also performed. We then investigated the correlation of serum HPSE, GSN, and SPARC levels with a cluster of clinical parameters including hemodynamic parameters, 6-min walking distance (6MWD), echocardiographic parameters, WHO functional class, and laboratory test. Changes to circulating serum proteins following balloon pulmonary angioplasty (BPA) and pulmonary endarterectomy (PEA) were assessed.

Results: We identified three proteins including heparanase (HPSE), gelsolin (GSN), and secreted protein acidic and rich in cysteine (SPARC) had significant changes in CTEPH. The receiver operating characteristic curve analysis showed that the areas under the curve of HPSE, GSN, and SPARC in CTEPH identification from control were 0.988, 0.776, and 0.698. Furthermore, HPSE was positively correlated with multiple parameters of right ventricular function such as right atrial transverse diameter, right ventricular basal diameter, right ventricular transverse diameter/left ventricular transverse diameter, glutamyl transpeptidase, D-dimer, uric acid, NT-proBNP. HPSE concentrations were significantly higher in patients with a low TAPSE/sPAP ratio (≤0.31 mm/mmHg) [65.4 (60.5,68.0) vs. 59.9(35.9,63.2) ng/ml, P< 0.05]. The treated CTEPH patient group had significantly lower HPSE levels after BPA.

Conclusion(s): Our finding demonstrates the potential value of HPSE in the individual assessment of disease severity, risk stratification, and therapeutic monitoring of CTEPH patients.