A Proteomics-Based Analysis of Blood Biomarkers for the Diagnosis of COPD Acute Exacerbation

Figures & data

Table 1 Clinical Characteristics of the 12 COPD Patients in the State of Exacerbation

Patient Number	Age	Gender	BMI	Smoking Status	FEV1 (%)	FVC (%)	FEV1/FVC (%)
1	71	Male	29.23	Former	63	71	58
2	71	Male	23.80	Current	47	73	44
3	64	Male	26.18	Former	49	99	37
4	84	Male	24.10	Former	47	80	36
5	68	Male	22.39	Never	42	94	32
6	66	Male	22.41	Current	68	112	44
7	76	Male	21.39	Current	67	98	46
8	75	Male	29.37	Former	26	54	32
9	69	Male	24.70	Former	34	82	29
10	64	Male	23.02	Former	64	72	66
11	58	Male	21.51	Former	40	86	36
12	65	Male	32.72	Former	59	81	51

Abbreviations: BMI, body mass index; FEV1, forced expiratory volume in one second; FVC, forced vital capacity.

Figure 1 Flow chart of the study.

Figure 2 Proteomic analysis of the plasma samples using SWATH-MS. (A) Boxplots of normalized plasma protein abundances in the 12 pairs of COPD patient samples. (B) Reproducibility of the SWATH-MS measurements. The graph shows the CVs of the peak areas detected in triplicate analyses of each sample.

Figure 3 Principal component analysis of protein abundances in plasma samples collected from the 12 patients in the AECOPD or convalescence state.

Table 2 The 29 Proteins That Were Differentially Expressed Between AECOPD and Convalescence Samples

Index	Protein Name	Up-Regulated in	Log2 Fold-Change (Convalescence/AECOPD)	q-Value
1	CRP	AECOPD	−3.29	2.62E-02
2	SAA1		−2.31	1.98E-04
3	FGA		−1.20	8.81E-03
4	DCD		−1.06	4.04E-02
5	LBP		−0.83	1.85E-03
6	C1QA		−0.72	1.19E-03
7	ORM2		−0.63	1.40E-04
8	KNG1		−0.61	8.81E-03
9	C9		−0.57	1.97E-04
10	APOC1		−0.56	1.98E-04
11	PROZ		−0.54	1.43E-02
12	ORM1		−0.49	1.85E-03
13	SERPINA3		−0.45	4.60E-03
14	CFI		−0.40	1.85E-03
15	APOA4	Convalescence	1.21	2.88E-03
16	IGHE		0.79	3.52E-02
17	APOC2		0.77	1.32E-04
18	HDAC4		0.73	1.42E-02
19	ITIH2		0.61	5.75E-05
20	MASP1		0.58	7.65E-03
21	F12		0.56	1.02E-03
22	SERPINA5		0.48	1.67E-03
23	ACTB		0.47	9.61E-03
24	TF		0.47	1.32E-04
25	APOL1		0.47	1.40E-04
26	RBP4		0.45	2.27E-02
27	ADSS2		0.42	4.38E-02
28	APOA2		0.40	8.33E-04
29	AFM		0.40	1.20E-03

Figure 4 Volcano plot and functional annotation of proteomic data from paired COPD plasma samples (N = 12). (A) A volcano plot showing the log2 fold-change in the abundance of each protein between the AECOPD and convalescence samples on the x-axis, and the FDR-corrected p-value (q-value) on the y-axis. Red circles show the 14 plasma proteins that were present at significantly higher levels in AECOPD samples than in convalescence samples. Blue circles show the 15 plasma proteins that were present at significantly higher levels in convalescence samples than in AECOPD samples. Gray circles represent plasma proteins that were not differentially expressed between the two groups. (B) A gene ontology (GO) analysis of the proteins that were differentially expressed between the two COPD states (FDR < 0.0001). The GO terms represent the link between a protein and a particular biological process, molecular function, or cellular component.

Figure 5 Boxplots of the plasma concentrations of SERPINA3 (A), ORM2 (B), and LBP (C) determined using ELISAs.