Journal article
Proteomic discovery analysis of quantitatively assessed emphysema in the general population. The MESA Lung Study
Respiratory research, Vol.26(1), 236
07/04/2025
DOI: 10.1186/s12931-025-03312-8
PMCID: PMC12228189
PMID: 40616090
Abstract
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.
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.
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.
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 (R
= 5.4%), improved overall model performance (R
= 24.8%), and uniquely explained greater variance in percent emphysema.
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.
Details
- Title: Subtitle
- Proteomic discovery analysis of quantitatively assessed emphysema in the general population. The MESA Lung Study
- Creators
- Daniel E Guzman - Columbia University Irving Medical CenterLisa Ruvuna - Cleveland ClinicClaire J Guo - Colorado School of Public HealthYifei Sun - Columbia University Irving Medical CenterKatherine A Pratte - National Jewish HealthAni W Manichaikul - University of VirginiaJohn S Kim - University of VirginiaWendy S Post - Johns Hopkins UniversityAlain G Bertoni - Wake Forest UniversityNorrina B Allen - Northwestern UniversityKarol E Watson - University of California, Los AngelesJames S Pankow - University of MinnesotaEric A Hoffman - University of IowaRuth F Dubin - The University of Texas Southwestern Medical CenterRajat Deo - University of PennsylvaniaIgor Z Barjaktarevic - University of California, Los AngelesEugene R Bleecker - University of ArizonaChristopher B Cooper - University of California, Los AngelesVictor E Ortega - Mayo Clinic in ArizonaAnnette T Hastie - Wake Forest UniversityRobert Paine III - University of UtahJames Michael Wells - University of MichiganJeffrey L Curtis - VA Ann Arbor Healthcare SystemEdwin K Silverman - Brigham and Women's HospitalPrescott G Woodruff - University of California, San FranciscoChristine Kim Garcia - Columbia University Irving Medical CenterJerome I Rotter - Harbor–UCLA Medical CenterRussell P Bowler - Cleveland ClinicPeter Ganz - University of California, San FranciscoR Graham Barr - Columbia University Irving Medical Center
- Resource Type
- Journal article
- Publication Details
- Respiratory research, Vol.26(1), 236
- DOI
- 10.1186/s12931-025-03312-8
- PMID
- 40616090
- PMCID
- PMC12228189
- NLM abbreviation
- Respir Res
- ISSN
- 1465-993X
- eISSN
- 1465-993X
- Publisher
- BMC
- Grant note
- 1R01HL137995 / NHLBI NIH HHS R01-HL077612 / NHLBI NIH HHS U01 HL137880 / NHLBI NIH HHS U01 HL089897 / NHLBI NIH HHS UL1-TR-000040 / NCATS NIH HHS 75N92023D00011 / NIH HHS R01HL159081 / NHLBI NIH HHS T32-HL144442 / NHLBI NIH HHS R01-HL130506 / NHLBI NIH HHS HHSN268200900013C-HHSN268200900020C / National Heart, Lung, and Blood Institute,United States
- Language
- English
- Date published
- 07/04/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Psychiatry; Internal Medicine
- Record Identifier
- 9984843746502771
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