{"title":"Exploratory Study of Prognostic Plasma Biomarkers in Patients with Pulmonary Arterial Hypertension.","authors":"Yukimitsu Kuwabara, Tetsuro Yokokawa, Sarah-Eve Lemay, Mélanie Sauvaget, Sandra Martineau, Sandra Breuils-Bonnet, François Potus, Sébastien Bonnet, Steeve Provencher, Olivier Boucherat","doi":"10.1016/j.ajpath.2025.04.018","DOIUrl":null,"url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular lumen occlusion, ultimately leading to right ventricular failure and death. Risk stratification is essential for the management of patients with PAH. So far, B-type natriuretic peptide and its N-terminal pro-form are the only circulating biomarkers used as part of composite PAH risk assessment tools. Identification of other biomarkers of vascular or systemic origin may also be valuable to provide additional information on disease severity and prognosis. Using proximity extension assay, >700 proteins related to oncology and neurology were measured in the plasma of 60 patients with PAH and 28 age- and sex-matched controls. Among the 114 proteins found to be significantly up-regulated in patients with PAH, 14 were independently associated with death/lung transplantation after adjustment for the 2015 European Society of Cardiology/European Respiratory Society, the REVEAL 2.0 risk scores, and the refined four-stratum risk assessment model. Among them, EDA2R, WFDC2, and TNFRSF10B displayed incremental prognostic value on top of these predictive models. Combining previously published proteomic data sets generated from different panels with the same cohort, a set of 23 proteins was identified, many of which are strongly associated with chronological age, that predict outcome of patients with PAH after adjusting for risk assessment tools. In conclusion, we identified proteins likely involved in the pathophysiology of the disease and potential candidates to prognostic enrichment.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":" ","pages":""},"PeriodicalIF":4.7000,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ajpath.2025.04.018","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular lumen occlusion, ultimately leading to right ventricular failure and death. Risk stratification is essential for the management of patients with PAH. So far, B-type natriuretic peptide and its N-terminal pro-form are the only circulating biomarkers used as part of composite PAH risk assessment tools. Identification of other biomarkers of vascular or systemic origin may also be valuable to provide additional information on disease severity and prognosis. Using proximity extension assay, >700 proteins related to oncology and neurology were measured in the plasma of 60 patients with PAH and 28 age- and sex-matched controls. Among the 114 proteins found to be significantly up-regulated in patients with PAH, 14 were independently associated with death/lung transplantation after adjustment for the 2015 European Society of Cardiology/European Respiratory Society, the REVEAL 2.0 risk scores, and the refined four-stratum risk assessment model. Among them, EDA2R, WFDC2, and TNFRSF10B displayed incremental prognostic value on top of these predictive models. Combining previously published proteomic data sets generated from different panels with the same cohort, a set of 23 proteins was identified, many of which are strongly associated with chronological age, that predict outcome of patients with PAH after adjusting for risk assessment tools. In conclusion, we identified proteins likely involved in the pathophysiology of the disease and potential candidates to prognostic enrichment.
期刊介绍:
The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.