Prognostic Biomarkers Based on Proteomic Technology in COPD: A Recent Review

Figures & data

Figure 1 An overview of proteomic technology.

Abbreviations: 2-DE, two-dimensional gel electrophoresis; 2D-DIGE, two-dimensional differential gel electrophoresis; SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis; IEC, ion-exchange chromatography; SEC, size-exclusion electrophoresis; SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis; IEC, ion-exchange chromatography; SEC, size-exclusion chromatography; SELDI-TOF-MS, surface-enhanced laser desorption/ionization-time of flight mass spectrometry; MALDI-TOF-MS, matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry; ESI-MS, electrospray ionization mass spectrometry; LC-MS/MS, liquid chromatography tandem-mass spectrometry; ICAT, isotope-coded affinity tags; ICPL, isotope-coded protein labels; iTRAQ, isobaric tag for relative and absolute quantitation; TMT, tandem mass tag; SILAC, stable isotope labeling by amino acids in cell culture; SC, spectral counting; XIC, extracted ion chromatograms; ELISA, enzyme-linked immunosorbent assay.

Table 1 COPD-Associated Proteomic Prognostic Biomarkers

Study	Source	Proteomic Approach	Subject	Number of Protein Identified	Main Finding and Description
Pratte et al^Citation45	Plasma	ELISA, LC-MS/MS	Including 4 cohorts: COPDGene (n = 1443); ECLIPSE (n = 2349); Pittsburgh COPD SCCOR (n = 399); SPIROMICS (n = 1623)	Not mentioned	Lower plasma sRAGE levels are associated with reduced FEV1 and exacerbation of emphysema
Bozinovski et al^Citation46	Serum	ELISA, SELDI-ToF	COPD patients (n=62)	1	SAA levels are positively correlated with COPD severity
Kim et al^Citation47	Plasma	LC-MS/MS, SWATH-MS, ELISA	AECOPD patients (n=12)	226	The expression of SERPINA3 was significantly upregulated in AECOPD compared to recovery phase.
Leung et al^Citation48	Plasma	MRM-MS, iTRAQ	Patients hospitalized with AECOPD: Cohort A(n = 72), Cohort B(n = 37), Cohort C(n = 109)	55	Biomarker scores for five proteins were significantly higher in the acute exacerbation phase than in the stable phase.
Diao et al^Citation49	Plasma	LC–MS/MS, iTRAQ, ELISA	Smokers without COPD (n=33), COPD patients (n=53)	636	THBG levels in COPD patients were elevated compared with those in controls, and ROCs also suggested that THBG could differentiate COPD patients from controls.
Diao et al^Citation50	Plasma	LC–MS/MS, iTRAQ, ELISA	Smokers without COPD (n=34), COPD patients (n=53)	830	Baseline FETUB can predict the occurrence of AE or frequent acute exacerbation and it showed a correlation trend with the number of acute exacerbation, indicating its levels have the potential to reflect the progression of COPD.
Beiko et al^Citation51	Serum	Multiplexed immunoassay	Patients with severe AATD (n=49)	317	Leptin, CRP, AFBP, and tPA were associated with baseline emphysema and all but leptin were associated with emphysema progression after controlling for age and sex.
Lv etc.^Citation52	BALF	ELISA	COPD group (n=85), healthy control group (n=20), AECOPD group (n=20)	2	The levels of SP-A and SP-D in BALF were positively correlated with lung function in COPD patients.
Hristova et al^Citation53	BALF	TMT, LC-MS/MS, ELISA	Ex-smoking mild/moderate COPD patients (n=26), healthy ex-smokers (n=20), nonsmokers (n=16)	Not mentioned	SP-A and SP-D concentrations were lower in COPD versus controls and correlated with lung function.
Yang et al^Citation54	BALF	iTRAQ	Nonsmokers (n = 17), smokers (n = 25)	506	Proteins in 2 pathways, phagosome and leukocyte transendothelial migration, were significantly correlated with the level of airway obstruction in smokers.
Dasgupta et al^Citation55	Sputum	LC-MS/MS, SWATH-MS	Asthma (n = 9), COPD (n = 13), chronic bronchitis (n = 5), healthy controls (n = 4)	855	The levels of eight proteins were significantly altered in exacerbator prone subjects compared to nonexacerbators. And total protein concentration in sputum which was significantly higher in frequent exacerbators.
Gao et al^Citation56	Sputum	2D-DIGE, MS, ELISA, Western blot; immunohistochemistry	Nonsmokers (n = 31), smokers (n = 169), COPD patients (n = 52)	1	The level of BPIFB1 in sputum correlates with lung function.
Mallia-Milanes et al^Citation57	Sputum	TAILS, LC-MS/MS	Stable COPD patients (n=9), AECOPD patients (n=9)	299	Acute exacerbation of COPD is associated with increased Elastase activity.
Ohlmerier et al^Citation58	Lung tissues	2D-DIGE, MS, ELISA, Western blot	Nonsmokers (n = 9), smokers (n = 9), COPD stage I–II (n = 8), COPD stage III–IV (n = 8), AATD (n = 8), IPF (n = 9)	82	TGM2 correlates with the severity of COPD.
Sun et al^Citation59	Lung tissues	TMT, LC-MS/MS, Western blot	Control (n=15), COPD frequent exacerbators (n=11), COPD infrequent exacerbators (n=23)	4506	The expression of three proteins, HLA-DQA1, PIGR, and Biglycan, was significantly higher in COPD patients with frequent exacerbations than in those with infrequent exacerbations.
Liu et al^Citation60	Lung tissues	TMT, LC-MS/MS, Western blot	COPD patients (n=3), Healthy individuals (n=20)	4976	Compared to the healthy individuals, COPD patients are more likely to have impaired hemostasis, which may impede the repair process of lung tissue.
Skerrett-Byrne et al^Citation61	Lung tissues	LC-MS/MS, iTRAQ	Cigarette smoke exposed mice (n=4), air exposed mice (n=4)	7324	The expression of HNRNPC, MSI2 and S100A1 correlated with the severity of COPD.
Ye et al^Citation62	Lung tissues	Immunohistochemistry, Western blot	Current-smoking patients (n = 15), patients with infrequent COPD exacerbations (n = 18), frequent COPD exacerbations (n = 8)	Not mentioned	AGR3 protein expression in lung tissues of patients with frequent COPD exacerbations was significantly lower than that of patients with infrequent COPD exacerbations.
Franciosi et al^Citation63	ELF	iTRAQ, ELISA, Immunohistochemistry	Young healthy individuals (n=5), young healthy non-susceptible individuals (n=5), old COPD patients (n=5), old healthy smokers (n=5), old healthy never-smokers (n=5)	6	Peroxiredoxin I, SerpinB3 and ALDH3A1, as protective proteins, are upregulated in COPD patients after smoking.
Qin et al^Citation64	Urine	LC-MS/MS, GO analysis	Cigarette smoke exposed rats (n=18), air exposed rats (n=18)	340	The expression of TFF2 was downregulated in the urine of COPD mice compared to the control group.

Abbreviations: ELISA, enzyme-linked immunosorbent assay; LC-MS/MS, liquid chromatography tandem-mass spectrometry; COPDGene, genetic epidemiology of COPD; ECLIPSE, evaluation of COPD longitudinally to identify predictive surrogate end-points; SCCOR, specialized center for clinically oriented research; SPIROMICS, subpopulations and intermediate outcome measures in COPD study; SELDI-ToF, surface-enhanced laser desorption ionization time-of-flight; SWATH-MS, sequential window acquisition of all theoretical-mass spectrometry; MRM-MS, multiple reaction monitoring-mass spectrometry; iTRAQ, isobaric tag for relative and absolute quantitation; THBG, thyroxine-binding globulin; ROC, receiver operating characteristic curve; FETUB, fetuin-B; CRP, c-reactive protein; AFBP, adipocyte fatty acid-binding protein; tPA, tissue plasminogen activator; BALF, bronchoalveolar lavage fluid; SP-A, lung surface active proteins A; SP-D, lung surface active proteins D; 2D-DIGE, two-dimensional differential gel electrophoresis; MS, mass spectrometry; TAILS, terminal amine isotopic labeling of substrates; AATD, α-1-antitrypsin deficiency; IPF, idiopathic pulmonary fibrosis; TMT, tandem mass tag; ELF, epithelial-lining fluid.

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