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Open Access 01-12-2024 | Biomarkers | Research

Serum proteome profiling reveals HGFA as a candidate biomarker for pulmonary arterial hypertension

Authors: Meng Zhang, Haobo Li, Shuangshuang Ma, Xincheng Li, Linfeng Xi, Yishan Li, Zhu Zhang, Shuai Zhang, Qian Gao, Qiang Huang, Jun Wan, Wanmu Xie, Jifeng Li, Peiran Yang, Yunxia Zhang, Zhenguo Zhai

Published in: Respiratory Research | Issue 1/2024

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Abstract

Background

Identification and validation of potential biomarkers could facilitate the identification of pulmonary arterial hypertension (PAH) and thus aid to study their roles in the disease process.

Methods

We used the isobaric tag for relative and absolute quantitation approaches to compare the protein profiles between the serum of PAH patients and the controls. Bioinformatics analyses and enzyme-linked immunosorbent assay (ELISA) identification of PAH patients and the controls were performed to identify the potential biomarkers. The receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic performance of these potential biomarkers. Mendelian randomization (MR) analysis further clarified the relationship between the potential biomarkers and PAH. Additionally, the expression levels of the potential biomarkers were further validated in two PAH animal models (monocrotaline-PH and Sugen5416 plus hypoxia-PH) using ELISA and reverse transcription-quantitative PCR (RT-qPCR).

Results

We identified significant changes in three proteins including heparanase (HPSE), gelsolin (GSN), and hepatocyte growth factor activator (HGFA) in PAH patients. The ROC analysis showed that the areas under the curve of HPSE, GSN, and HGFA in differentiating PAH patients from controls were 0.769, 0.777, and 0.964, respectively. HGFA was correlated with multiple parameters of right ventricular functions in PAH patients. Besides proteomic analysis, we also used MR method to demonstrate the causal link between genetically reduced HGFA levels and an increased risk of PAH. In subsequent validation study in PAH animal models, the mRNA expression levels of HGFA in the lung tissues were significantly lower in PAH rat models than in controls. In the rat models, serum levels of HGFA were lower compared to the control group and showed a negative correlation with right ventricular systolic pressure.

Conclusion

The study demonstrated that HGFA might be a promising biomarker for noninvasive detection of PAH.
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Metadata
Title
Serum proteome profiling reveals HGFA as a candidate biomarker for pulmonary arterial hypertension
Authors
Meng Zhang
Haobo Li
Shuangshuang Ma
Xincheng Li
Linfeng Xi
Yishan Li
Zhu Zhang
Shuai Zhang
Qian Gao
Qiang Huang
Jun Wan
Wanmu Xie
Jifeng Li
Peiran Yang
Yunxia Zhang
Zhenguo Zhai
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2024
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-024-03036-1

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