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

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

doi:10.1186/s12931-024-03036-1

Respiratory Research (Nov 2024)

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

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

Affiliations

Meng Zhang: Department of Pulmonary and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University
Haobo Li: National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital
Shuangshuang Ma: National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital
Xincheng Li: National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital
Linfeng Xi: National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital
Yishan Li: National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital
Zhu Zhang: National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital
Shuai Zhang: National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital
Qian Gao: National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital
Qiang Huang: National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital
Jun Wan: Department of Pulmonary and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University
Wanmu Xie: National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital
Jifeng Li: Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University; Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing Chao-Yang Hospital, Capital Medical University; Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University; Department of Respiratory Disease, Capital Medical University
Peiran Yang: State Key Laboratory of Respiratory Health and Multimorbidity, Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College; National Center for Respiratory Medicine; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; National Clinical Research Center for Respiratory Diseases
Yunxia Zhang: National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital
Zhenguo Zhai: National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital

DOI: https://doi.org/10.1186/s12931-024-03036-1
Journal volume & issue: Vol. 25, no. 1
pp. 1 – 14

Abstract

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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.

Published in Respiratory Research

ISSN: 1465-9921 (Print); 1465-993X (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the respiratory system
Website: https://respiratory-research.biomedcentral.com/

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