An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study Prof Toby M Maher, PhD, Eunice.

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An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study Prof Toby M Maher, PhD, Eunice Oballa, MSc, Juliet K Simpson, PhD, Joanne Porte, MSc, Anthony Habgood, BSc, William A Fahy, MD, Aiden Flynn, PhD, Philip L Molyneaux, PhD, Rebecca Braybrooke, RGN, Hrushikesh Divyateja, MSc, Helen Parfrey, MD, Doris Rassl, MD, Anne-Marie Russell, BSc, Gauri Saini, MD, Elisabetta A Renzoni, PhD, Anne-Marie Duggan, MSc, Prof Richard Hubbard, DM, Prof Athol U Wells, MD, Pauline T Lukey, PhD, Richard P Marshall, PhD, Prof R Gisli Jenkins, PhD The Lancet Respiratory Medicine Volume 5, Issue 12, Pages 946-955 (December 2017) DOI: 10.1016/S2213-2600(17)30430-7 Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 1 Study cohort profiles The Lancet Respiratory Medicine 2017 5, 946-955DOI: (10.1016/S2213-2600(17)30430-7) Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 2 Multiplex discovery analysis (A) Fold change of biomarker in patients with IPF compared with healthy controls. (B) FDR of biomarker in patients with IPF compared with healthy controls using the Benjamini-Hochberg procedure. (C) Effect of progression group in mixed-effects model examining the effect of visit, progression group, interaction between visit and progression group adjusted for age, site, sex, and smoking status in patients with progressive IPF compared with patients with stable IPF. (D) FDR of biomarker comparing patients with stable IPF with patients with progressive IPF using Benjamini-Hochberg procedure. (E) Risk of mortality in patients with rising concentrations of biomarkers after 3 months, compared with stable or falling concentrations of biomarkers. (F) FDR of biomarker comparing effect of rising concentrations of biomarkers after three months versus stable concentrations of biomarker on overall survival using Benjamini-Hochberg procedure. FDR=false discovery rate. IPF=idiopathic pulmonary fibrosis. MMP7=matrix metalloproteinase 7. SP-D=surfactant protein D. The Lancet Respiratory Medicine 2017 5, 946-955DOI: (10.1016/S2213-2600(17)30430-7) Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 3 Immunohistochemistry of lung tissue Tissue samples stained with anti-CA-125 antibody obtained from (A) non-IPF controls and (B) patients with IPF. Tissue samples stained with CA19-9 antibody obtained from (C) non-IPF controls and (D) patients with IPF. IPF=idiopathic pulmonary fibrosis. The Lancet Respiratory Medicine 2017 5, 946-955DOI: (10.1016/S2213-2600(17)30430-7) Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 4 Biomarker serum concentrations in patients with progressive and stable disease Serum concentrations of the four biomarkers assessed in the validation cohort in patients with progressive disease (red bars) and stable disease (blue bars) assessed at baseline and 3 months. (A) SP-D, (B) MMP7, (C) CA19-9, and (D) CA-125. Points show mean values and bars show SDs. MMP7=matrix metalloproteinase 7. SP-D=surfactant protein D. The Lancet Respiratory Medicine 2017 5, 946-955DOI: (10.1016/S2213-2600(17)30430-7) Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 5 Risk of overall mortality by biomarker concentrations at 3 months Red lines show rising biomarker concentrations and blue lines show stable or falling concentrations. (A) CA-125, (B) CA19-9, (C) MMP7, and (D) SP-D. Overall survival was adjusted for age, sex, and smoking status. The date of censoring was April 4, 2016. MMP7=matrix metalloproteinase 7. SP-D=surfactant protein D. The Lancet Respiratory Medicine 2017 5, 946-955DOI: (10.1016/S2213-2600(17)30430-7) Copyright © 2017 Elsevier Ltd Terms and Conditions