دورية أكاديمية
Proteomic Biomarkers of Survival in Idiopathic Pulmonary Fibrosis.
| العنوان: | Proteomic Biomarkers of Survival in Idiopathic Pulmonary Fibrosis. |
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| المؤلفون: | Oldham JM; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine.; Department of Epidemiology, and., Huang Y; Division of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, Virginia., Bose S; Department of Biostatistics, University of Michigan, Ann Arbor, Michigan., Ma SF; Division of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, Virginia., Kim JS; Division of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, Virginia., Schwab A; Division of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, Virginia., Ting C; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine., Mou K; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine., Lee CT; Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois., Adegunsoye A; Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois., Ghodrati S; Division of Pulmonary, Critical Care and Sleep Medicine, University of California, Davis, Davis, California., Pugashetti JV; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine., Nazemi N; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine., Strek ME; Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois., Linderholm AL; Division of Pulmonary, Critical Care and Sleep Medicine, University of California, Davis, Davis, California., Chen CH; Division of Pulmonary, Critical Care and Sleep Medicine, University of California, Davis, Davis, California., Murray S; Department of Biostatistics, University of Michigan, Ann Arbor, Michigan., Zemans RL; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine., Flaherty KR; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine.; Pulmonary Fibrosis Foundation, Chicago, Illinois; and., Martinez FJ; Weill Cornell Medical Center, New York, New York., Noth I; Division of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, Virginia. |
| المصدر: | American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2024 May 01; Vol. 209 (9), pp. 1111-1120. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Thoracic Society Country of Publication: United States NLM ID: 9421642 Publication Model: Print Cited Medium: Internet ISSN: 1535-4970 (Electronic) Linking ISSN: 1073449X NLM ISO Abbreviation: Am J Respir Crit Care Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2000- : New York, NY : American Thoracic Society Original Publication: New York, NY : American Lung Association, c1994- |
| مواضيع طبية MeSH: | Idiopathic Pulmonary Fibrosis*/mortality , Idiopathic Pulmonary Fibrosis*/blood , Biomarkers*/blood , Proteomics*, Humans ; Male ; Female ; Middle Aged ; Aged ; Prognosis ; Proportional Hazards Models ; Prospective Studies ; Cohort Studies |
| مستخلص: | Rationale: Idiopathic pulmonary fibrosis (IPF) causes progressive lung scarring and high mortality. Reliable and accurate prognostic biomarkers are urgently needed. Objectives: To identify and validate circulating protein biomarkers of IPF survival. Methods: High-throughput proteomic data were generated using prospectively collected plasma samples from patients with IPF from the Pulmonary Fibrosis Foundation Patient Registry (discovery cohort) and the Universities of California, Davis; Chicago; and Virginia (validation cohort). Proteins associated with three-year transplant-free survival (TFS) were identified using multivariable Cox proportional hazards regression. Those associated with TFS after adjustment for false discovery in the discovery cohort were advanced for testing in the validation cohort, with proteins maintaining TFS association with consistent effect direction considered validated. After combining cohorts, functional analyses were performed, and machine learning was used to derive a proteomic signature of TFS. Measurements and Main Results: Of 2,921 proteins tested in the discovery cohort ( n = 871), 231 were associated with differential TFS. Of these, 140 maintained TFS association with consistent effect direction in the validation cohort ( n = 355). After cohorts were combined, the validated proteins with the strongest TFS association were latent-transforming growth factor β-binding protein 2 (hazard ratio [HR], 2.43; 95% confidence interval [CI] = 2.09-2.82), collagen α-1(XXIV) chain (HR, 2.21; 95% CI = 1.86-2.39), and keratin 19 (HR, 1.60; 95% CI = 1.47-1.74). In decision curve analysis, a proteomic signature of TFS outperformed a similarly derived clinical prediction model. Conclusions: In the largest proteomic investigation of IPF outcomes performed to date, we identified and validated 140 protein biomarkers of TFS. These results shed important light on potential drivers of IPF progression. |
| التعليقات: | Comment in: Am J Respir Crit Care Med. 2024 May 1;209(9):1056-1057. doi: 10.1164/rccm.202311-2108ED. (PMID: 38117693) |
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| معلومات مُعتمدة: | K23 HL146942 United States HL NHLBI NIH HHS; T32 HL007605 United States HL NHLBI NIH HHS; R35HL160770 United States HL NHLBI NIH HHS; UG3HL145266 United States HL NHLBI NIH HHS; R35 HL160770 United States HL NHLBI NIH HHS; K23HL150301 United States HL NHLBI NIH HHS; R01 HL130796 United States HL NHLBI NIH HHS; R01 HL169166 United States HL NHLBI NIH HHS; UG3 HL145266 United States HL NHLBI NIH HHS; K23HL146942 United States HL NHLBI NIH HHS; T32 HL007749 United States HL NHLBI NIH HHS; UH3 HL145266 United States HL NHLBI NIH HHS; K23 HL150301 United States HL NHLBI NIH HHS; T32HL007749 United States HL NHLBI NIH HHS; T32HL007605 United States HL NHLBI NIH HHS; RO1HL130796 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: IPF; interstitial lung disease; proteomics; survival; transplant |
| المشرفين على المادة: | 0 (Biomarkers) |
| تواريخ الأحداث: | Date Created: 20231017 Date Completed: 20240501 Latest Revision: 20240801 |
| رمز التحديث: | 20240801 |
| مُعرف محوري في PubMed: | PMC11092951 |
| DOI: | 10.1164/rccm.202301-0117OC |
| PMID: | 37847691 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1535-4970 |
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| DOI: | 10.1164/rccm.202301-0117OC |