Chronic obstructive pulmonary disease (COPD) biomarkers and uses thereof
Methods, compositions, and kits for predicting whether a subject with chronic obstructive pulmonary disease (COPD) or at risk of developing COPD is likely to have progressive COPD are provided. Methods, compositions, and kits for predicting whether lung function is likely to decline in a subject with COPD or at risk for developing COPD are also provided.
1. A method of predicting whether lung function will decline in a subject with chronic obstructive pulmonary disease (COPD) or at risk of developing COPD, comprising detecting the level of at least one biomarker protein selected from SIGLEC7, IGFBP1, GPC2, LYVE1, PSPN, CCDC80, IGFBP-7, PIGR, ANGPT2, GSK3β, LTA LTB, FGF19, CCL5, THPO, MST1R, CHST15, COL18A1, FST, HS6ST1, LGALS3, IL10, and LGMN in a sample from the subject, wherein lung function is predicted to decline if the level of SIGLEC7, IGFBP1, LYVE1, PIGR, ANGPT2, GSK3β, CCDC80, CHST15, COL18A1, CCL5, FST, LGALS3, or LGMN is higher than a control level of the respective biomarker protein, and wherein lung function is predicted to decline if the level of GPC2, PSPN, LTA LTB, FGF19, THPO, MST1R, HS6ST1, or IL10 is lower than a control level of the respective biomarker protein, wherein the detecting comprises:
(i) contacting proteins of the sample with a set of aptamers, wherein each aptamer of the set of aptamers specifically binds to a different biomarker protein being detected;
(ii) separating aptamers that are bound to biomarker protein from aptamers that are not bound to biomarker protein; and
(iii) detecting the separated aptamers;
thereby detecting the level of the at least one biomarker protein in the sample.
2. The method of claim 1 , further comprising detecting the level of at least one biomarker protein selected from IGFBP2, HSPA1A, SLPI, CXCL5, SOD2, CCL22, FGFR2, and IGFBP4 in a sample from the subject, wherein lung function is predicted to decline if the level of IGFBP2, HSPA1A, SLPI, SOD2, CCL22, or IGFBP4 is higher than a control level of the respective biomarker, and wherein lung function is predicted to decline if the level of CXCL5 or FGFR2 is lower than a control level of the respective protein.
3. The method of claim 1 , wherein the method comprises detecting SIGLEC7 and CCL5.
4. The method of claim 3 , wherein the method comprises detecting the level of at least one biomarker selected from SIGLEC7, CCL5, and IGFBP1.
5. The method of claim 4 , wherein the method comprises detecting the levels of at least two biomarkers selected from SIGLEC7, CCL5, IGFBP2, LTA LTB, PSPN, GSK3β, and IGFBP1.
6. The method of claim 4 , wherein the method comprises detecting SIGLEC7, IGFBP2, CCL5, IGFBP1, LTA LTB, and PSPN.
7. The method of claim 1 , wherein at least one aptamer is a slow off-rate aptamer.
8. The method of claim 7 , wherein at least one slow off-rate aptamer comprises at least one nucleotide with a modification.
9. The method of claim 7 , wherein each slow off-rate aptamer binds to its target protein with an off rate (t 1/2 ) of ≧30 minutes.
10. The method of claim 1 , wherein the sample is a blood sample.
11. The method of claim 10 , wherein the sample is selected from a serum sample and a plasma sample.
12. The method of claim 1 , wherein the method further comprises treating the subject for COPD.
13. The method of claim 12 , wherein treating the subject for COPD comprises at least one treatment selected from a smoking cessation program, a long-acting bronchodilator, an inhaled corticosteroid, and a systemic corticosteroid.
14. The method of claim 13 , wherein the smoking cessation program comprises a therapeutic agent that aids in smoking cessation, behavior modification therapy, or both.
15. The method of claim 13 , wherein the long-acting bronchodilator is selected from a β2-agonist and an anticholinergic.
16. The method of claim 15 , wherein the β2-agonist is selected from salmeterol, formoterol, bambuterol, and indacaterol; and the anticholinergic is selected from tiotropium and ipratropium bromide.
17. The method of claim 13 , wherein the inhaled corticosteroid is selected from beclomethasone, budesonide, flunisolide, fluticasone, mometasone, and triamcinolone.
18. The method of claim 13 , wherein the systemic corticosteroid is selected from methylprednisolone, prednisolone, and prednisone.
19. The method of claim 1 , wherein detecting the separated aptamers comprises at least one method selected from amplification and hybridization.