Proteomic discovery analysis of quantitatively assessed emphysema in the general population. The MESA Lung Study
Abstract Background Pulmonary emphysema occurs frequently in older adults, often without airflow limitation. Its presence predicts symptoms, respiratory hospitalizations and deaths, and all-cause mortality. Proteomics may provide further insights into emphysema pathogenesis and inform therapeutic ta...
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2025-07-01
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| Online Access: | https://doi.org/10.1186/s12931-025-03312-8 |
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| author | Daniel E. Guzman Lisa Ruvuna Claire J. Guo Yifei Sun Katherine A. Pratte Ani W. Manichaikul John S. Kim Wendy S. Post Alain G. Bertoni Norrina B. Allen Karol E. Watson James S. Pankow Eric A. Hoffman Ruth F. Dubin Rajat Deo Igor Z. Barjaktarevic Eugene R. Bleecker Christopher B. Cooper Victor E. Ortega Annette T. Hastie Robert Paine James Michael Wells Jeffrey L. Curtis Edwin K. Silverman Prescott G. Woodruff Christine Kim Garcia Jerome I. Rotter Russell P. Bowler Peter Ganz R. Graham Barr |
| author_facet | Daniel E. Guzman Lisa Ruvuna Claire J. Guo Yifei Sun Katherine A. Pratte Ani W. Manichaikul John S. Kim Wendy S. Post Alain G. Bertoni Norrina B. Allen Karol E. Watson James S. Pankow Eric A. Hoffman Ruth F. Dubin Rajat Deo Igor Z. Barjaktarevic Eugene R. Bleecker Christopher B. Cooper Victor E. Ortega Annette T. Hastie Robert Paine James Michael Wells Jeffrey L. Curtis Edwin K. Silverman Prescott G. Woodruff Christine Kim Garcia Jerome I. Rotter Russell P. Bowler Peter Ganz R. Graham Barr |
| author_sort | Daniel E. Guzman |
| collection | DOAJ |
| description | Abstract Background Pulmonary emphysema occurs frequently in older adults, often without airflow limitation. Its presence predicts symptoms, respiratory hospitalizations and deaths, and all-cause mortality. Proteomics may provide further insights into emphysema pathogenesis and inform therapeutic targets. Objective We performed a proteomic discovery analysis of percent emphysema on computed tomography (CT) in a population-based, multiethnic sample from the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study. Replication was performed in two chronic obstructive pulmonary disease (COPD)-based studies, the SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) and the Genetic Epidemiology of COPD (COPDGene) Study. Methods MESA recruited participants from the general population in 2000–02. The MESA Lung Study performed full-lung CT scans in 2010–12. Percent emphysema was defined as the percentage of lung voxels < -950 Hounsfield units. Over 7,200 plasma aptamers were measured via SomaScan. Cross-sectional linear and least absolute shrinkage and selection operator (LASSO) regression models were adjusted for demographics, anthropometrics, smoking, renal function, and scanner parameters. Statistical significance was defined as a false discovery rate p-value < 0.05. Gene Ontology (GO)/Reactome enrichment analyses were performed. LASSO-selected proteins’ predictive performance was evaluated. Results Among 2,504 participants in the MESA Lung Study, mean age was 69.4 years, 1,291 had ever smoked, and median percent emphysema-like lung was 1.4%. In total, 1,234 aptamers were significantly associated with percent emphysema in the MESA Lung Study, and 35 replicated in the SPIROMICS and COPDGene Studies. Novel associations included protein family with sequence similarity (FAM) 177A1, syntenin-2, ubiquitin carboxyl-terminal hydrolase 25, and uncharacterized protein C20orf173. Previously identified emphysema-associated proteins included soluble advanced glycosylation end product-specific receptor (sRAGE), protein S100-A12, high mobility group protein B1, and roundabout homolog 2. Enrichment analyses identified 40 GO biological processes, including chemokine production and regulation and cell–cell adhesion and regulation, and two Reactome pathways, including RAGE signaling. In tenfold cross-validation, novel proteins were largely retained by LASSO (R2 = 5.4%), improved overall model performance (R2 = 24.8%), and uniquely explained greater variance in percent emphysema. Conclusions This analysis in a general population sample identified novel and previously characterized proteins whose functional roles were validated by GO/Reactome enriched pathways, offering new insights into emphysema pathophysiology and therapeutics. |
| format | Article |
| id | doaj-art-8971247848c045b8a1bd9de6fc4e0c29 |
| institution | Kabale University |
| issn | 1465-993X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj-art-8971247848c045b8a1bd9de6fc4e0c292025-08-20T03:37:40ZengBMCRespiratory Research1465-993X2025-07-0126111510.1186/s12931-025-03312-8Proteomic discovery analysis of quantitatively assessed emphysema in the general population. The MESA Lung StudyDaniel E. Guzman0Lisa Ruvuna1Claire J. Guo2Yifei Sun3Katherine A. Pratte4Ani W. Manichaikul5John S. Kim6Wendy S. Post7Alain G. Bertoni8Norrina B. Allen9Karol E. Watson10James S. Pankow11Eric A. Hoffman12Ruth F. Dubin13Rajat Deo14Igor Z. Barjaktarevic15Eugene R. Bleecker16Christopher B. Cooper17Victor E. Ortega18Annette T. Hastie19Robert Paine20James Michael Wells21Jeffrey L. Curtis22Edwin K. Silverman23Prescott G. Woodruff24Christine Kim Garcia25Jerome I. Rotter26Russell P. Bowler27Peter Ganz28R. Graham Barr29Department of Medicine, Columbia University Irving Medical CenterGenomic Medicine Institute, Cleveland ClinicDepartment of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical CampusDepartment of Medicine, Columbia University Irving Medical CenterNational Jewish HealthCenter for Public Health, University of Virginia School of MedicineDepartment of Medicine, Columbia University Irving Medical CenterDepartment of Medicine, Johns Hopkins University School of MedicineDivision of Public Health Sciences, Wake Forest University School of MedicineCenter for Epidemiology and Population Health, Northwestern UniversityDepartment of Medicine, University of California, Los Angeles David Geffen School of MedicineDivision of Epidemiology and Community Health, School of Public Health, University of MinnesotaDepartment of Radiology, Carver College of Medicine, University of IowaDepartment of Medicine, University of Texas SouthwesternDepartment of Medicine, University of PennsylvaniaDepartment of Medicine, University of California, Los Angeles David Geffen School of MedicineDepartment of Medicine, The University of Arizona Health SciencesDepartment of Medicine, University of California, Los Angeles David Geffen School of MedicineDepartment of Medicine, Division of Pulmonary Medicine, Mayo ClinicDepartment of Medicine, Wake Forest School of MedicineDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, University of Utah School of MedicineDepartment of Medicine, University of MichiganDepartment of Medicine, University of MichiganChanning Division of Network Medicine and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s HospitalDepartment of Medicine, University of California San FranciscoDepartment of Medicine, Columbia University Irving Medical CenterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterGenomic Medicine Institute, Cleveland ClinicDepartment of Medicine, University of California San FranciscoDepartment of Medicine, Columbia University Irving Medical CenterAbstract Background Pulmonary emphysema occurs frequently in older adults, often without airflow limitation. Its presence predicts symptoms, respiratory hospitalizations and deaths, and all-cause mortality. Proteomics may provide further insights into emphysema pathogenesis and inform therapeutic targets. Objective We performed a proteomic discovery analysis of percent emphysema on computed tomography (CT) in a population-based, multiethnic sample from the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study. Replication was performed in two chronic obstructive pulmonary disease (COPD)-based studies, the SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) and the Genetic Epidemiology of COPD (COPDGene) Study. Methods MESA recruited participants from the general population in 2000–02. The MESA Lung Study performed full-lung CT scans in 2010–12. Percent emphysema was defined as the percentage of lung voxels < -950 Hounsfield units. Over 7,200 plasma aptamers were measured via SomaScan. Cross-sectional linear and least absolute shrinkage and selection operator (LASSO) regression models were adjusted for demographics, anthropometrics, smoking, renal function, and scanner parameters. Statistical significance was defined as a false discovery rate p-value < 0.05. Gene Ontology (GO)/Reactome enrichment analyses were performed. LASSO-selected proteins’ predictive performance was evaluated. Results Among 2,504 participants in the MESA Lung Study, mean age was 69.4 years, 1,291 had ever smoked, and median percent emphysema-like lung was 1.4%. In total, 1,234 aptamers were significantly associated with percent emphysema in the MESA Lung Study, and 35 replicated in the SPIROMICS and COPDGene Studies. Novel associations included protein family with sequence similarity (FAM) 177A1, syntenin-2, ubiquitin carboxyl-terminal hydrolase 25, and uncharacterized protein C20orf173. Previously identified emphysema-associated proteins included soluble advanced glycosylation end product-specific receptor (sRAGE), protein S100-A12, high mobility group protein B1, and roundabout homolog 2. Enrichment analyses identified 40 GO biological processes, including chemokine production and regulation and cell–cell adhesion and regulation, and two Reactome pathways, including RAGE signaling. In tenfold cross-validation, novel proteins were largely retained by LASSO (R2 = 5.4%), improved overall model performance (R2 = 24.8%), and uniquely explained greater variance in percent emphysema. Conclusions This analysis in a general population sample identified novel and previously characterized proteins whose functional roles were validated by GO/Reactome enriched pathways, offering new insights into emphysema pathophysiology and therapeutics.https://doi.org/10.1186/s12931-025-03312-8ProteomicsBiomarkersEmphysema |
| spellingShingle | Daniel E. Guzman Lisa Ruvuna Claire J. Guo Yifei Sun Katherine A. Pratte Ani W. Manichaikul John S. Kim Wendy S. Post Alain G. Bertoni Norrina B. Allen Karol E. Watson James S. Pankow Eric A. Hoffman Ruth F. Dubin Rajat Deo Igor Z. Barjaktarevic Eugene R. Bleecker Christopher B. Cooper Victor E. Ortega Annette T. Hastie Robert Paine James Michael Wells Jeffrey L. Curtis Edwin K. Silverman Prescott G. Woodruff Christine Kim Garcia Jerome I. Rotter Russell P. Bowler Peter Ganz R. Graham Barr Proteomic discovery analysis of quantitatively assessed emphysema in the general population. The MESA Lung Study Respiratory Research Proteomics Biomarkers Emphysema |
| title | Proteomic discovery analysis of quantitatively assessed emphysema in the general population. The MESA Lung Study |
| title_full | Proteomic discovery analysis of quantitatively assessed emphysema in the general population. The MESA Lung Study |
| title_fullStr | Proteomic discovery analysis of quantitatively assessed emphysema in the general population. The MESA Lung Study |
| title_full_unstemmed | Proteomic discovery analysis of quantitatively assessed emphysema in the general population. The MESA Lung Study |
| title_short | Proteomic discovery analysis of quantitatively assessed emphysema in the general population. The MESA Lung Study |
| title_sort | proteomic discovery analysis of quantitatively assessed emphysema in the general population the mesa lung study |
| topic | Proteomics Biomarkers Emphysema |
| url | https://doi.org/10.1186/s12931-025-03312-8 |
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