Six-SOMAmer Index Relating to Immune, Protease and Angiogenic Functions Predicts Progression in IPF

PLoS One. 2016 Aug 4;11(8):e0159878. doi: 10.1371/journal.pone.0159878. eCollection 2016.


Rationale: Biomarkers in easily accessible compartments like peripheral blood that can predict disease progression in idiopathic pulmonary fibrosis (IPF) would be clinically useful regarding clinical trial participation or treatment decisions for patients. In this study, we used unbiased proteomics to identify relevant disease progression biomarkers in IPF.

Methods: Plasma from IPF patients was measured using an 1129 analyte slow off-rate modified aptamer (SOMAmer) array, and patient outcomes were followed over the next 80 weeks. Receiver operating characteristic (ROC) curves evaluated sensitivity and specificity for levels of each biomarker and estimated area under the curve (AUC) when prognostic biomarker thresholds were used to predict disease progression. Both logistic and Cox regression models advised biomarker selection for a composite disease progression index; index biomarkers were weighted via expected progression-free days lost during follow-up with a biomarker on the unfavorable side of the threshold.

Results: A six-analyte index, scaled 0 to 11, composed of markers of immune function, proteolysis and angiogenesis [high levels of ficolin-2 (FCN2), cathepsin-S (Cath-S), legumain (LGMN) and soluble vascular endothelial growth factor receptor 2 (VEGFsR2), but low levels of inducible T cell costimulator (ICOS) or trypsin 3 (TRY3)] predicted better progression-free survival in IPF with a ROC AUC of 0.91. An index score ≥ 3 (group ≥ 2) was strongly associated with IPF progression after adjustment for age, gender, smoking status, immunomodulation, forced vital capacity % predicted and diffusing capacity for carbon monoxide % predicted (HR 16.8, 95% CI 2.2-126.7, P = 0.006).

Conclusion: This index, derived from the largest proteomic analysis of IPF plasma samples to date, could be useful for clinical decision making in IPF, and the identified analytes suggest biological processes that may promote disease progression.

MeSH terms

  • Aged
  • Area Under Curve
  • Biomarkers / blood
  • Cathepsins / metabolism
  • Cysteine Endopeptidases / metabolism
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis / immunology
  • Idiopathic Pulmonary Fibrosis / metabolism
  • Idiopathic Pulmonary Fibrosis / pathology*
  • Inducible T-Cell Co-Stimulator Protein / metabolism
  • Lectins / metabolism
  • Logistic Models
  • Male
  • Middle Aged
  • Peptide Hydrolases / metabolism*
  • Proportional Hazards Models
  • ROC Curve
  • Severity of Illness Index*
  • Smoking
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism


  • Biomarkers
  • Inducible T-Cell Co-Stimulator Protein
  • Lectins
  • ficolin
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • Cathepsins
  • Peptide Hydrolases
  • Cysteine Endopeptidases
  • asparaginylendopeptidase