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ABSTRACT: Rationale
Identification and validation of circulating biomarkers for lung function decline in COPD remains an unmet need.Objective
Identify prognostic and dynamic plasma protein biomarkers of COPD progression.Methods
We measured plasma proteins using SomaScan from two COPD-enriched cohorts, the Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene), and one population-based cohort, Multi-Ethnic Study of Atherosclerosis (MESA) Lung. Using SPIROMICS as a discovery cohort, linear mixed models identified baseline proteins that predicted future change in FEV1 (prognostic model) and proteins whose expression changed with change in lung function (dynamic model). Findings were replicated in COPDGene and MESA-Lung. Using the COPD-enriched cohorts, Gene Set Enrichment Analysis (GSEA) identified proteins shared between COPDGene and SPIROMICS. Metascape identified significant associated pathways.Measurements and main results
The prognostic model found 7 significant proteins in common (p < 0.05) among all 3 cohorts. After applying false discovery rate (adjusted p < 0.2), leptin remained significant in all three cohorts and growth hormone receptor remained significant in the two COPD cohorts. Elevated baseline levels of leptin and growth hormone receptor were associated with slower rate of decline in FEV1. Twelve proteins were nominally but not FDR significant in the dynamic model and all were distinct from the prognostic model. Metascape identified several immune related pathways unique to prognostic and dynamic proteins.Conclusion
We identified leptin as the most reproducible COPD progression biomarker. The difference between prognostic and dynamic proteins suggests disease activity signatures may be different from prognosis signatures.
SUBMITTER: Ruvuna L
PROVIDER: S-EPMC11326337 | biostudies-literature | 2024 Aug
REPOSITORIES: biostudies-literature
Ruvuna Lisa L Hijazi Kahkeshan K Guzman Daniel E DE Guo Claire C Loureiro Joseph J Khokhlovich Edward E Morris Melody M Obeidat Ma'en M Pratte Katherine A KA DiLillo Katarina M KM Sharma Sunita S Kechris Katerina K Anzueto Antonio A Barjaktarevic Igor I Bleecker Eugene R ER Casaburi Richard R Comellas Alejandro A Cooper Christopher B CB DeMeo Dawn L DL Foreman Marilyn M Flenaugh Eric L EL Han MeiLan K MK Hanania Nicola A NA Hersh Craig P CP Krishnan Jerry A JA Labaki Wassim W WW Martinez Fernando J FJ O'Neal Wanda K WK Paine Robert R Peters Stephen P SP Woodruff Prescott G PG Wells J Michael JM Wendt Christine H CH Arnold Kelly B KB Barr R Graham RG Curtis Jeffrey L JL Ngo Debby D Bowler Russell P RP
medRxiv : the preprint server for health sciences 20240808
<h4>Rationale</h4>Identification and validation of circulating biomarkers for lung function decline in COPD remains an unmet need.<h4>Objective</h4>Identify prognostic and dynamic plasma protein biomarkers of COPD progression.<h4>Methods</h4>We measured plasma proteins using SomaScan from two COPD-enriched cohorts, the Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene), and one population-based cohort, Multi-Ethnic Study of Ath ...[more]