Introduction
Material and methods
Patient population
Digital evaluation score system
Isolation of PBMC RNA
Microarray analysis
Data analysis
Results
Clinical informatics analysis
Groups | Subject no. | Age (yr) | Smoking status | FEV 1/FVC% | FEV 1/pred% | Goddard emphysema score |
---|---|---|---|---|---|---|
Control | 1 | 56 | Nonsmoker | 75 | 85 | 0 |
2 | 53 | Nonsmoker | 80 | 87 | 0 | |
3 | 62 | Nonsmoker | 77 | 91 | 0 | |
4 | 68 | Nonsmoker | 81 | 83 | 0 | |
5 | 58 | Nonsmoker | 79 | 81 | 0 | |
6 | 67 | Nonsmoker | 76 | 90 | 0 | |
Mean ± SE | 60.7 ± 2.5 | 78.0 ± 1.0 | 86.2 ± 1.6 | 0.0 ± 0.0 | ||
Stable COPD | 1 | 71 | Ex-smoker | 57 | 47 | 10 |
2 | 75 | Ex-smoker | 46 | 66 | 6 | |
3 | 61 | Ex-smoker | 46 | 47 | 8 | |
4 | 57 | Ex-smoker | 38 | 29 | 12 | |
5 | 59 | Ex-smoker | 67 | 66 | 7 | |
6 | 53 | Ex-smoker | 29 | 36 | 11 | |
Mean ± SE | 62.7 ± 3.5 | 47.2 ± 5.5 | 48.5 ± 6.2 | 9.0 ± 1.0 | ||
AECOPD | 1 | 77 | Ex-smoker | 40 | 42 | 10 |
2 | 72 | Ex-smoker | 36 | 27 | 11 | |
3 | 65 | Ex-smoker | 28 | 33 | 16 | |
4 | 56 | Ex-smoker | 48 | 61 | 6 | |
5 | 61 | Ex-smoker | 69 | 55 | 4 | |
6 | 67 | Ex-smoker | 56 | 60 | 8 | |
Mean ± SE | 66.3 ± 3.1 | 46.2 ± 6.0 | 46.3 ± 5.9 | 9.2 ± 1.7 |
DESS scores | |||||
---|---|---|---|---|---|
Patient no. | Control | Stable COPD | AE-1 | AE-3 | AE-10 |
1 | 0 | 30 | 100 | 78 | 43 |
2 | 4 | 27 | 81 | 66 | 46 |
3 | 8 | 35 | 86 | 76 | 36 |
4 | 4 | 55 | 70 | 51 | 30 |
5 | 3 | 38 | 80 | 71 | 35 |
6 | 0 | 47 | 97 | 81 | 30 |
Mean ± SE | 3.2 ± 1.2 | 38.7 ± 4.3 | 85.7 ± 4.6 | 70.5 ± 4.5 | 36.7 ± 2.7 |
Gene expression profiles
Fold changes in upregulated genes ( n ) | |||||||||
---|---|---|---|---|---|---|---|---|---|
Comparisons | >2 | >5 | >8 | >10 | >15 | >20 | >30 | >50 | >100 |
Stable vs Con | 4,508 | 671 | 217 | 145 | 49 | 27 | 9 | 1 | 0 |
AE-1 vs Con | 3,899 | 734 | 334 | 221 | 136 | 86 | 40 | 18 | 3 |
AE-3 vs Con | 4,167 | 742 | 358 | 259 | 149 | 97 | 51 | 17 | 5 |
AE-10 vs Con | 3,488 | 677 | 331 | 238 | 116 | 74 | 35 | 10 | 1 |
AE-1 vs Stable | 4,067 | 389 | 135 | 80 | 36 | 21 | 9 | 3 | 1 |
AE-3 vs Stable | 5,063 | 620 | 221 | 146 | 56 | 24 | 10 | 1 | 0 |
AE-10 vs Stable | 5,451 | 534 | 178 | 117 | 56 | 33 | 14 | 1 | 0 |
AE-3 vs AE-1 | 586 | 8 | 2 | 2 | 0 | 0 | 0 | 0 | 0 |
AE-10 vs AE-1 | 1,735 | 164 | 55 | 26 | 10 | 4 | 1 | 0 | 0 |
AE-10 vs AE-3 | 1,706 | 156 | 49 | 29 | 2 | 2 | 1 | 0 | 0 |
Stable vs control | AE-1 vs control | AE-3 vs control | AE-10 vs control | ||||
---|---|---|---|---|---|---|---|
Fold changes | Genes | Fold changes | Genes | Fold changes | Genes | Fold changes | Genes |
31.7 |
REXO1L2P
| 30.3 |
HP
| 30.1 |
FOS
| 30.8 |
EMP2
|
33.0 |
DEFA1
| 30.5 |
LOC152573
| 30.6 |
BPIL1
| 31.0 |
SEPP1
|
33.3 |
DUB3
| 31.2 |
INHBA
| 31.0 |
ARG1
| 31.0 |
FOLR1
|
37.2 |
LOC402207
| 31.4 |
COL6A3
| 31.6 |
N/A
| 31.1 |
GPX3
|
37.3 |
DUB3
| 32.4 |
MPO
| 31.9 |
LOC152573
| 31.2 |
SFTPB
|
40.5 |
LOC402110
| 32.6 |
ELF3
| 32.5 |
COL6A3
| 31.4 |
S100A14
|
43.1 |
LOC653600
| 34.4 |
CLDN4
| 32.9 |
TIMP3
| 33.1 |
FOLR1
|
43.5 |
N/A
| 34.9 |
DCN
| 33.5 |
FOS
| 33.4 |
CDH5
|
50.7 |
MGC45438
| 35.7 |
CTGF
| 34.4 |
KRT19
| 34.9 |
CAV1
|
35.7 |
MMP2
| 34.7 |
INHBA
| 35.4 |
DLC1
| ||
36.2 |
MFAP4
| 35.2 |
HP
| 35.6 |
FOSB
| ||
37.1 |
EPB42
| 35.6 |
CD177
| 36.1 |
KRT19
| ||
37.2 |
H19
| 36.5 |
LCN2
| 36.4 |
SUSD2
| ||
37.3 |
ATP1B1
| 36.9 |
CTGF
| 36.9 |
FN1
| ||
37.5 |
INHBA
| 37.9 |
MMP8
| 37.2 |
ADH1C
| ||
38.0 |
AZU1
| 38.3 |
ORM1
| 37.2 |
RNASE1
| ||
38.5 |
LCN2
| 38.8 |
ELF3
| 37.3 |
IL1RL1
| ||
39.6 |
CEACAM8
| 38.9 |
DCN
| 41.1 |
FOLR1
| ||
40.3 |
CALCA
| 39.0 |
CTSG
| 41.3 |
DHCR24
| ||
41.4 |
LOC387763
| 39.1 |
CLDN4
| 41.3 |
LOC387763
| ||
42.2 |
CEACAM3
| 39.3 |
CALCA
| 42.0 |
ADH1B
| ||
45.9 |
UNQ473
| 40.0 |
DCN
| 43.6 |
LAMA3
| ||
54.0 |
BPIL1
| 40.1 |
FOSB
| 45.0 |
GPX3
| ||
56.2 |
FN1
| 41.1 |
ATP1B1
| 47.9 |
DCN
| ||
56.7 |
CEACAM5
| 41.6 |
MFAP4
| 49.1 |
EPAS1
| ||
58.4 |
MMP8
| 41.8 |
FN1
| 50.9 |
CNN3
| ||
65.0 |
CALCA
| 42.0 |
MMP2
| 51.5 |
DCN
| ||
66.3 |
BPI
| 42.0 |
GPR97
| 54.5 |
LOC653509
| ||
68.7 |
DEFA1
| 42.2 |
INHBA
| 56.2 |
CXCL2
| ||
72.3 |
COL1A2
| 45.5 |
AZU1
| 58.2 |
MGC45438
| ||
77.2 |
CA1
| 46.0 |
BPI
| 58.5 |
CYP4B1
| ||
80.2 |
PLUNC
| 46.4 |
LOC387763
| 59.3 |
CTGF
| ||
83.0 |
CEACAM1
| 46.6 |
MPO
| 75.8 |
GPRC5A
| ||
83.9 |
DEFA4
| 50.0 |
HP
| 88.9 |
TIMP3
| ||
85.0 |
COL3A1
| 50.7 |
ORM2
| 149.5 |
MFAP4
| ||
96.1 |
DEFA1
| 53.1 |
UNQ473
| ||||
99.4 |
CEACAM5
| 57.8 |
AQP9
| ||||
101.2 |
CEACAM1
| 59.6 |
CEACAM5
| ||||
115.8 |
LOC653600
| 59.6 |
BPIL1
| ||||
140.3 |
DEFA4
| 61.0 |
CEACAM1
| ||||
62.8 |
DEFA1
| ||||||
66.5 |
CEACAM1
| ||||||
72.6 |
DEFA4
| ||||||
82.5 |
PLUNC
| ||||||
86.7 |
DEFA1
| ||||||
92.9 |
COL1A2
| ||||||
100.8 |
CEACAM5
| ||||||
101.1 |
CALCA
| ||||||
109.4 |
LOC653600
| ||||||
111.5 |
COL3A1
| ||||||
165.7 |
DEFA4
|
Stable vs control | AE-1 vs control | AE-3 vs control | AE-10 vs control | ||||
---|---|---|---|---|---|---|---|
Fold changes | Genes | Fold changes | Gene | Fold changes | Genes | Fold changes | Genes |
20.1 |
P8
| 20.3 |
PLAU
| 20.0 |
ALPL
| 20.3 |
SCNN1A
|
20.1 |
REXO1L5P
| 21.0 |
COL6A3
| 20.1 |
MUC1
| 20.4 |
MGC45438
|
20.2 |
UNQ473
| 21.1 |
SLC25A37
| 20.2 |
SPDEF
| 20.7 |
FBLN1
|
20.2 |
DEFA1
| 21.1 |
HIG2
| 20.3 |
HIG2
| 20.7 |
CLDN4
|
20.5 |
LOC440015
| 21.2 |
GPRC5A
| 20.4 |
KLK11
| 20.9 |
SFTPA2
|
21.1 |
LOC391749
| 21.2 |
CFB
| 20.4 |
MGP
| 21.0 |
FKBP9
|
21.3 |
MGC45438
| 21.3 |
LTF
| 20.4 |
GPR109A
| 21.1 |
FAM107A
|
21.7 |
RP11-146D12.2
| 21.4 |
VSIG4
| 21.0 |
LOC653342
| 21.3 |
N/A
|
22.0 |
LOC399839
| 21.7 |
FOSB
| 21.1 |
CFB
| 21.4 |
C10orf10
|
22.9 |
SPDEF
| 21.9 |
SLC25A37
| 21.3 |
P8
| 21.5 |
SELENBP1
|
23.0 |
CLDN4
| 22.0 |
ARG1
| 21.8 |
PBEF1
| 21.6 |
ANXA3
|
24.7 |
LOC349196
| 22.0 |
SPDEF
| 21.9 |
S100P
| 21.6 |
IFI27
|
25.3 |
STAC2
| 22.2 |
LTF
| 21.9 |
MS4A3
| 21.8 |
C1QC
|
25.8 |
REXO1L3P
| 22.3 |
FOS
| 22.4 |
COL6A3
| 21.9 |
SEPP1
|
26.3 |
SCGB3A1
| 22.6 |
FAM46C
| 23.1 |
MANSC1
| 22.0 |
KLK11
|
26.9 |
RNASE1
| 22.6 |
ISLR
| 23.2 |
COL1A2
| 22.1 |
P8
|
27.0 |
AZGP1
| 22.6 |
COL1A2
| 23.2 |
GCA
| 22.1 |
LOC653723
|
29.5 |
H19
| 22.8 |
ATP1B1
| 23.3 |
LTBP2
| 22.5 |
LOC391359
|
23.8 |
SCNN1A
| 23.9 |
CHI3L1
| 22.7 |
LAMB2
| ||
23.8 |
SERPINE1
| 24.0 |
TMC5
| 22.8 |
AQP1
| ||
23.8 |
EPB42
| 24.2 |
CD24
| 24.0 |
C9orf61
| ||
23.8 |
C1QC
| 24.2 |
HP
| 24.1 |
C4BPA
| ||
23.9 |
RGS1
| 24.3 |
ISLR
| 24.2 |
LTBP2
| ||
23.9 |
ORM2
| 24.3 |
SIX1
| 24.3 |
UNQ473
| ||
24.1 |
COL5A1
| 24.5 |
APOE
| 24.5 |
TMEM139
| ||
24.5 |
MS4A3
| 24.6 |
COL3A1
| 24.6 |
N/A
| ||
25.6 |
CD177
| 24.6 |
LOC646309
| 25.7 |
OLFML3
| ||
25.6 |
APOE
| 24.7 |
CEACAM3
| 25.9 |
SNF1LK
| ||
26.4 |
C20orf114
| 24.9 |
AATK
| 25.9 |
A2M
| ||
26.6 |
BPIL1
| 25.3 |
LTF
| 26.4 |
FXYD3
| ||
27.1 |
CTSG
| 25.4 |
ALPL
| 27.0 |
HP
| ||
27.4 |
FOS
| 25.6 |
ACSL1
| 27.1 |
N/A
| ||
27.6 |
ALAS2
| 26.2 |
CEACAM6
| 27.4 |
LOC653509
| ||
28.0 |
INHBA
| 26.3 |
COL5A1
| 28.0 |
LDB2
| ||
28.0 |
TIMP3
| 26.4 |
KLK11
| 28.0 |
OLFML3
| ||
28.1 |
COL3A1
| 26.7 |
PRTN3
| 28.5 |
SFTPA1
| ||
28.1 |
SLC4A1
| 26.9 |
RGS1
| 28.6 |
MUC1
| ||
28.2 |
KLK11
| 27.3 |
KCNJ15
| 29.6 |
HSPA12B
| ||
28.2 |
LOC653492
| 27.4 |
CAMP
| 29.8 |
MFAP4
| ||
28.5 |
LOC203510
| 27.6 |
PLAU
| ||||
28.7 |
CEACAM3
| 27.8 |
LTF
| ||||
28.8 |
DCN
| 27.9 |
ANXA3
| ||||
28.9 |
CEACAM1
| 28.0 |
H19
| ||||
29.0 |
CEACAM6
| 28.0 |
SERPINE1
| ||||
29.3 |
SELENBP1
| 28.1 |
LTF
| ||||
29.7 |
KRT19
| 28.3 |
INHBA
|
Stable vs control | AE-1 vs control | AE-3 vs control | AE-10 vs control | ||||
---|---|---|---|---|---|---|---|
Fold changes | Genes | Fold changes | Genes | Fold changes | Genes | Fold changes | Genes |
15.2 |
LOC645558
| 15.0 |
CNN3
| 15.0 |
GPR109B
| 15.0 |
USP54
|
15.7 |
N/A
| 15.0 |
GPT2
| 15.0 |
LOC653492
| 15.0 |
MGC45438
|
15.9 |
LOC653455
| 15.1 |
ORM1
| 15.2 |
RNASE1
| 15.2 |
SLCO2A1
|
15.9 |
DUX4
| 15.1 |
LOC402110
| 15.3 |
FN1
| 15.3 |
AGER
|
16.1 |
LOC653768
| 15.1 |
MDK
| 15.5 |
ACSL1
| 15.3 |
FLJ11259
|
16.5 |
RAB17
| 15.2 |
ELF3
| 15.5 |
CDH5
| 15.5 |
CLEC3B
|
16.6 |
LOC653541
| 15.2 |
PSG8
| 15.6 |
FOLR3
| 15.8 |
ADCY4
|
16.6 |
LOC391763
| 15.3 |
SLC25A37
| 15.8 |
PVRL2
| 16.0 |
FN1
|
16.7 |
LOC642286
| 15.4 |
FKBP9
| 15.9 |
KRT19
| 16.1 |
HP
|
16.7 |
S100A14
| 15.5 |
C1QB
| 15.9 |
MDK
| 16.1 |
CKB
|
16.7 |
NBPF9
| 15.6 |
BPGM
| 16.0 |
APOC1
| 16.1 |
CYP4B1
|
16.9 |
PSG8
| 15.7 |
AQP9
| 16.3 |
NOL3
| 16.2 |
RARRES2
|
17.0 |
REXO1L6P
| 15.7 |
LOC402207
| 16.3 |
ATP1B1
| 16.3 |
TSPAN1
|
17.0 |
MLPH
| 15.7 |
PSG11
| 16.4 |
TMC4
| 16.6 |
SDC4
|
17.1 |
FAM90A7
| 16.0 |
KLK11
| 16.4 |
VEGF
| 16.7 |
ERG
|
17.4 |
LOC401650
| 16.2 |
KIAA0703
| 16.6 |
SPAG4
| 16.8 |
LOC653107
|
17.8 |
DUB3
| 16.2 |
IGFBP5
| 16.8 |
LIF
| 17.2 |
RAB25
|
17.9 |
MGC45438
| 16.2 |
IGFBP3
| 16.8 |
CCDC80
| 17.2 |
COL1A2
|
18.9 |
COL3A1
| 16.2 |
N/A
| 16.9 |
CEACAM3
| 17.3 |
DCN
|
19.1 |
LOC645732
| 16.2 |
SLC25A37
| 16.9 |
IGFBP3
| 17.5 |
TSPAN13
|
19.8 |
LOC392188
| 16.3 |
SIX1
| 17.1 |
CXCL2
| 17.6 |
HSD17B6
|
20.0 |
MUC1
| 16.3 |
LOC645009
| 17.2 |
FKBP9
| 17.8 |
RHOB
|
16.4 |
C1QA
| 17.2 |
CEACAM1
| 17.9 |
KRT19
| ||
16.5 |
UBD
| 17.7 |
ELF3
| 18.0 |
AQP9
| ||
16.6 |
LOC653342
| 17.7 |
CNN3
| 18.2 |
FOLR1
| ||
17.0 |
GPR97
| 17.8 |
PGLYRP1
| 18.2 |
IL1RL1
| ||
17.1 |
COL1A1
| 17.9 |
KRT23
| 18.2 |
SERPING1
| ||
17.3 |
ALPL
| 18.1 |
SLC44A4
| 18.3 |
MGC35295
| ||
17.4 |
FBLN1
| 18.1 |
SCNN1A
| 18.4 |
FLJ43663
| ||
17.5 |
HIG2
| 18.4 |
FBLN1
| 18.6 |
TGM2
| ||
17.7 |
COL8A1
| 18.5 |
HPR
| 18.6 |
ADH1C
| ||
17.9 |
TMC5
| 18.6 |
SYT7
| 18.7 |
KIAA1026
| ||
18.1 |
LTBP2
| 18.6 |
CEACAM8
| 19.1 |
DKFZP686A01247
| ||
18.4 |
SLC25A37
| 18.8 |
C1R
| 19.2 |
CCDC48
| ||
18.7 |
CEACAM3
| 18.8 |
COL1A1
| 19.2 |
ANKRD25
| ||
18.9 |
MPO
| 18.9 |
COL8A1
| 19.3 |
DMBT1
| ||
19.0 |
CD24
| 18.9 |
C1QC
| 19.4 |
MALL
| ||
19.0 |
CHI3L1
| 18.9 |
SFRP2
| 19.5 |
ANXA8
| ||
19.0 |
DCN
| 19.0 |
HIG2
| 19.5 |
SPRY4
| ||
19.1 |
P8
| 19.2 |
C1QB
| 19.7 |
ELF3
| ||
19.1 |
CEACAM6
| 19.2 |
GPRC5A
| 19.9 |
EHD2
| ||
19.1 |
ACSL1
| 19.3 |
MMP25
| 20.0 |
DCN
| ||
19.5 |
PRTN3
| 19.3 |
UBD
| ||||
19.5 |
LIF
| 19.3 |
GADD45A
| ||||
19.6 |
LTF
| 19.4 |
ISLR
| ||||
19.7 |
ANXA3
| 19.5 |
ORM1
| ||||
19.7 |
C1R
| 19.5 |
C20orf114
| ||||
19.7 |
MUC1
| 19.5 |
LOC203510
| ||||
19.8 |
PSG4
| 19.6 |
DCN
| ||||
19.9 |
HP
| 19.7 |
FN1
| ||||
19.8 |
DAAM2
| ||||||
19.9 |
FOLR3
|
AE-1 vs stable | AE-3 vs stable | AE-10 vs stable | |||
---|---|---|---|---|---|
Fold changes | Genes | Fold changes | Genes | Fold changes | Genes |
37.3 |
MMP8
| 33.2 |
LOC646309
| 30.0 |
CCDC48
|
37.6 |
CEACAM5
| 34.7 |
SERPINE1
| 31.9 |
LOC653509
|
38.6 |
PLUNC
| 34.9 |
FOS
| 32.0 |
EPAS1
|
39.4 |
BPIL1
| 37.6 |
CYR61
| 32.2 |
CDH5
|
40.3 |
CYR61
| 39.5 |
CEACAM5
| 34.4 |
CLDN5
|
45.4 |
CEACAM5
| 39.6 |
PLUNC
| 36.3 |
SEPP1
|
55.2 |
CALCA
| 40.1 |
ARG1
| 38.7 |
CAV1
|
56.0 |
VSIG4
| 43.5 |
BPIL1
| 39.2 |
CYR61
|
103.9 |
CA1
| 46.0 |
CEACAM5
| 42.1 |
ADH1B
|
85.9 |
CALCA
| 44.2 |
CTGF
| ||
44.9 |
CAV1
| ||||
45.1 |
GPRC5A
| ||||
49.8 |
SEPP1
| ||||
81.4 |
GPX3
|
AE-1 vs stable | AE-3 vs stable | AE-10 vs stable | |||
---|---|---|---|---|---|
Fold changes | Genes | Fold changes | Genes | Fold changes | Genes |
20.1 |
MS4A3
| 20.5 |
GPR97
| 20.3 |
TIMP3
|
21.0 |
CEACAM6
| 20.6 |
ALPL
| 20.3 |
SLC6A4
|
21.1 |
SLC25A37
| 20.7 |
MTHFS
| 20.4 |
SFTPA2
|
21.2 |
DCN
| 21.0 |
FLJ32028
| 20.6 |
AKAP2
|
22.4 |
SPP1
| 21.4 |
ADM
| 20.7 |
DST
|
24.0 |
TCN1
| 23.3 |
ACSL1
| 21.2 |
TCF21
|
24.7 |
BPIL1
| 23.3 |
DCN
| 21.5 |
ADH1C
|
26.4 |
SLC25A37
| 24.3 |
MMP8
| 21.6 |
SLIT3
|
26.6 |
CTGF
| 24.5 |
TCN1
| 21.7 |
C9orf61
|
28.5 |
ARG1
| 25.3 |
FOS
| 22.5 |
FOSB
|
28.6 |
FOS
| 25.3 |
FOSB
| 25.5 |
MFAP4
|
29.5 |
SERPINE1
| 27.5 |
CTGF
| 26.0 |
GPX3
|
28.3 |
BPIL1
| 26.5 |
DCN
| ||
28.4 |
VSIG4
| 26.9 |
SFTPB
| ||
27.6 |
FBLN5
| ||||
28.1 |
LOC653509
| ||||
28.5 |
ADH1C
| ||||
28.7 |
SFTPA1
| ||||
28.7 |
TIMP3
|
AE-1 vs stable | AE-3 vs stable | AE-10 vs stable | |||
---|---|---|---|---|---|
Fold changes | Genes | Fold changes | Genes | Fold changes | Genes |
15.6 |
ADM
| 15.2 |
LOC387763
| 15.0 |
VSIG4
|
15.8 |
DEFA4
| 15.2 |
MMP25
| 15.6 |
IL1RL1
|
16.2 |
DEFA4
| 15.3 |
USP15
| 15.8 |
PZP
|
16.2 |
C1R
| 15.5 |
C1R
| 16.0 |
LDB2
|
16.9 |
GPNMB
| 15.8 |
KCNJ15
| 16.2 |
FLJ43663
|
17.2 |
DCN
| 15.9 |
GADD45A
| 16.5 |
N/A
|
17.3 |
FAM46C
| 15.9 |
LRRC4
| 16.6 |
CD55
|
17.6 |
ALAS2
| 16.3 |
GLT1D1
| 16.8 |
CXCL2
|
17.6 |
CALCA
| 16.4 |
CD55
| 16.9 |
IL1RL1
|
17.9 |
GPNMB
| 16.5 |
CEACAM6
| 17.0 |
RHOB
|
18.2 |
DUSP1
| 16.6 |
SPP1
| 17.1 |
DLC1
|
18.2 |
CEACAM6
| 16.7 |
SLC25A37
| 17.2 |
VIPR1
|
18.2 |
SLC25A37
| 17.1 |
ORM1
| 17.2 |
CRYAB
|
18.7 |
FOS
| 17.2 |
CALCA
| 17.8 |
CNN3
|
18.9 |
SLC25A37
| 17.3 |
DUSP1
| 18.1 |
DCN
|
17.5 |
CD177
| 18.1 |
IFI27
| ||
17.6 |
GPNMB
| 18.2 |
SLIT2
| ||
17.7 |
MS4A3
| 18.3 |
RASIP1
| ||
17.8 |
DCN
| 18.8 |
MFAP4
| ||
17.8 |
GPR109A
| 19.0 |
CAMK2N1
| ||
17.9 |
BASP1
| 19.0 |
CD55
| ||
17.9 |
IL8RB
| 19.5 |
AGER
| ||
18.4 |
AQP9
| 19.9 |
DKFZP686A01247
| ||
18.7 |
DEFA4
| ||||
18.8 |
QPCT
| ||||
19.0 |
PBEF1
| ||||
19.0 |
BASP1
| ||||
19.0 |
CEACAM6
| ||||
19.2 |
GNG10
| ||||
19.7 |
GPNMB
| ||||
19.7 |
GCA
| ||||
20.0 |
RNASE3
|
AE-3 vs AE-1 | AE-10 vs AE-1 | AE-10 vs AE-3 | |||
---|---|---|---|---|---|
Fold changes | Genes | Fold changes | Genes | Fold changes | Genes |
5.1 |
TMEM50A
| 10.3 |
SUSD2
| 10.1 |
SLCO2A1
|
5.2 |
BCL2A1
| 10.6 |
TCF21
| 10.1 |
OAS3
|
5.3 |
C6orf32
| 10.6 |
FOLR1
| 10.1 |
C4BPA
|
6.0 |
PI3
| 10.7 |
C9orf61
| 10.2 |
DMBT1
|
7.0 |
KCNJ15
| 10.9 |
LOC653107
| 10.4 |
VSIG2
|
7.6 |
CISH
| 11.3 |
AGER
| 10.4 |
LOC653107
|
10.4 |
CISH
| 12.0 |
SLIT2
| 10.5 |
ITLN2
|
10.7 |
CISH
| 12.7 |
ITLN2
| 10.7 |
CX3CR1
|
12.9 |
FLRT3
| 10.7 |
MSLN
| ||
13.1 |
VIPR1
| 10.8 |
SOCS2
| ||
13.2 |
SOCS2
| 10.9 |
LOC653107
| ||
13.3 |
IL1RL1
| 11.7 |
FOLR1
| ||
13.4 |
LOC653107
| 11.7 |
GPX3
| ||
13.8 |
C4BPA
| 11.8 |
CLIC5
| ||
14.4 |
CYP4B1
| 11.8 |
SLIT2
| ||
14.4 |
LAMA3
| 11.9 |
LOC653107
| ||
15.1 |
CYP4B1
| 12.1 |
AQP1
| ||
15.2 |
ADH1C
| 12.6 |
LOC653509
| ||
15.7 |
MGC35295
| 12.6 |
ADH1C
| ||
15.8 |
GPX3
| 12.7 |
ADH1C
| ||
17.0 |
IL1RL1
| 12.8 |
ADH1B
| ||
17.9 |
MSLN
| 12.9 |
LAMA3
| ||
20.0 |
ADH1C
| 13.6 |
IL1RL1
| ||
22.4 |
ADH1B
| 13.6 |
CYP4B1
| ||
24.5 |
SLC6A4
| 13.9 |
FAM107A
| ||
35.3 |
FOLR1
| 14.2 |
LOC653107
| ||
14.9 |
CYP4B1
| ||||
22.0 |
MGC35295
| ||||
31.2 |
SLC6A4
|
Fold changes in upregulated genes ( n ) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Compared pairs | >2 | >5 | >6 | >8 | >10 | >15 | >20 | >30 | >50 | >100 |
Stable vs Con | 4,516 | 135 | 55 | 9 | 4 | 2 | 1 | 0 | 0 | 0 |
AE-1 vs Con | 2,975 | 182 | 107 | 47 | 22 | 7 | 4 | 1 | 0 | 0 |
AE-3 vs Con | 3,426 | 225 | 149 | 65 | 35 | 11 | 5 | 2 | 0 | 0 |
AE-10 vs Con | 2,798 | 124 | 73 | 31 | 16 | 2 | 1 | 1 | 0 | 0 |
AE-1 vs Stable | 3,207 | 33 | 16 | 4 | 4 | 2 | 0 | 0 | 0 | 0 |
AE-3 vs Stable | 4,510 | 125 | 71 | 21 | 8 | 3 | 1 | 0 | 0 | 0 |
AE-10 vs Stable | 5,288 | 445 | 236 | 97 | 49 | 20 | 8 | 3 | 0 | 0 |
AE-3 vs AE-1 | 598 | 32 | 23 | 17 | 5 | 3 | 2 | 0 | 0 | 0 |
AE-10 vs AE-1 | 2,162 | 261 | 168 | 82 | 43 | 21 | 14 | 10 | 5 | 1 |
AE-10 vs AE-3 | 1,918 | 192 | 130 | 66 | 36 | 15 | 9 | 6 | 4 | 0 |
Stable vs Con | AE-1 vs Con | AE-3 vs Con | AE-10 vs Con | ||||
---|---|---|---|---|---|---|---|
Fold changes | Genes | Fold changes | Genes | Fold changes | Genes | Fold changes | Genes |
10.7 |
EIF3S6
| 10.3 |
HAND1
| 10.2 |
GZMK
| 10.0 |
C21orf7
|
10.7 |
YLPM1
| 10.3 |
CD8B
| 10.5 |
CXCR3
| 10.0 |
NELL2
|
16.1 |
TFCP2L1
| 10.4 |
UBASH3A
| 10.6 |
AK5
| 10.4 |
C21orf7
|
21.0 |
SCP2
| 10.8 |
TRA@
| 10.7 |
TRA@
| 10.4 |
GFI1B
|
10.9 |
TRBV3-1
| 10.7 |
IL24
| 10.5 |
LOC129293
| ||
11.2 |
CD8B
| 10.9 |
CD6
| 10.5 |
LOC123876
| ||
11.4 |
MAL
| 10.9 |
N/A
| 10.7 |
HIST1H3H
| ||
11.4 |
LOC643514
| 11.2 |
KIAA0748
| 11.1 |
IL24
| ||
11.5 |
NELL2
| 11.4 |
LCK
| 11.4 |
GFI1B
| ||
11.7 |
TTC24
| 11.5 |
CD8B
| 11.9 |
CRTAC1
| ||
12.7 |
CD8B
| 12.3 |
APBB1
| 11.9 |
OR10A4
| ||
13.1 |
LEF1
| 12.3 |
IL12RB1
| 11.9 |
SAA3P
| ||
13.8 |
TCF7
| 12.5 |
TTC24
| 12.7 |
TTC24
| ||
14.2 |
LOC129293
| 12.5 |
GFI1B
| 14.9 |
TFCP2L1
| ||
14.5 |
LOC129293
| 12.5 |
CRTAC1
| 18.6 |
SCP2
| ||
15.6 |
TCF7
| 12.6 |
TRBV3-1
| 32.3 |
UNQ470
| ||
16.1 |
TCF7
| 12.6 |
ATG9B
| ||||
16.8 |
CD8B
| 12.9 |
ABLIM1
| ||||
21.8 |
TFCP2L1
| 12.9 |
LOC129293
| ||||
25.4 |
CRTAC1
| 13.0 |
CD8B
| ||||
27.9 |
SCP2
| 13.1 |
CD28
| ||||
44.1 |
UNQ470
| 13.1 |
GRAP2
| ||||
14.3 |
UBASH3A
| ||||||
14.4 |
CCR7
| ||||||
15.0 |
LOC129293
| ||||||
16.0 |
CD8B
| ||||||
18.1 |
UNQ470
| ||||||
18.7 |
SCP2
| ||||||
18.8 |
LEF1
| ||||||
19.3 |
LEF1
| ||||||
23.5 |
CD8B
| ||||||
24.3 |
TCF7
| ||||||
25.1 |
TCF7
| ||||||
30.4 |
TCF7
| ||||||
32.0 |
TFCP2L1
|
Stable vs Con | AE-1 vs Con | AE-3 vs Con | AE-10 vs Con | ||||
---|---|---|---|---|---|---|---|
Fold changes | Genes | Fold changes | Genes | Fold changes | Genes | Fold changes | Genes |
8.2 |
AK5
| 8.1 |
CD3G
| 8.0 |
TRBV19
| 8.1 |
HFE2
|
8.6 |
TRA@
| 8.2 |
LY9
| 8.0 |
OTOA
| 8.2 |
TRA@
|
9.1 |
ZC3HAV1
| 8.2 |
AK5
| 8.1 |
CD7
| 8.6 |
UNQ470
|
9.3 |
MAL
| 8.2 |
C21orf7
| 8.1 |
GRAP2
| 8.6 |
CD248
|
9.7 |
TMEM50B
| 8.2 |
TRBC1
| 8.1 |
TNFRSF25
| 8.6 |
XG
|
8.3 |
ANKDD1A
| 8.2 |
C21orf7
| 8.7 |
ATG9B
| ||
8.4 |
CD6
| 8.2 |
EPHA6
| 8.8 |
LOC339778
| ||
8.4 |
RPS6KB1
| 8.2 |
GIMAP5
| 8.9 |
TCF7
| ||
8.5 |
TMEM50B
| 8.3 |
1-Sep
| 8.9 |
CCR7
| ||
8.7 |
YLPM1
| 8.3 |
UBASH3A
| 9.2 |
LOC644663
| ||
8.7 |
TRBV19
| 8.4 |
GIMAP7
| 9.4 |
LOC129293
| ||
8.8 |
FLT3LG
| 8.5 |
MGC23244
| 9.5 |
MGC39606
| ||
8.9 |
N/A
| 8.6 |
LOC645852
| 9.7 |
GZMK
| ||
9.1 |
LEF1
| 8.7 |
SCAP1
| 9.9 |
AK5
| ||
9.1 |
GZMK
| 9.0 |
HIST1H3H
| 9.9 |
TCF7
| ||
9.1 |
KIAA0748
| 9.0 |
HFE2
| ||||
9.2 |
ABLIM1
| 9.2 |
GFI1B
| ||||
9.5 |
C21orf7
| 9.2 |
TMEM50B
| ||||
9.5 |
ATG9B
| 9.5 |
N/A
| ||||
9.6 |
LCK
| 9.5 |
C21orf7
| ||||
9.6 |
LOC647353
| 9.6 |
GATA3
| ||||
9.8 |
CCR7
| 9.7 |
C21orf7
| ||||
9.8 |
UNQ470
| 9.7 |
CD247
| ||||
9.9 |
OR10A4
| 9.8 |
LCK
| ||||
9.9 |
IL12RB1
| 9.8 |
KSP37
| ||||
9.9 |
FAIM3
| ||||||
9.9 |
SPOCK2
| ||||||
9.9 |
TRA@
| ||||||
9.9 |
SH2D1B
| ||||||
10.0 |
GRAP2
|
Stable vs Con | AE-1 vs Con | AE-3 vs Con | AE-10 vs Con | ||||
---|---|---|---|---|---|---|---|
Fold changes | Genes | Fold changes | Genes | Fold changes | Genes | Fold changes | Genes |
6.0 |
NDUFV3
| 6.0 |
MAL
| 6.0 |
IL7R
| 6.0 |
HKDC1
|
6.0 |
C17orf45
| 6.0 |
ARHGAP12
| 6.0 |
CD28
| 6.1 |
TANC2
|
6.1 |
MAL
| 6.0 |
TRAPPC4
| 6.0 |
KIR2DS1
| 6.1 |
FAM5B
|
6.1 |
CXCR6
| 6.0 |
GNLY
| 6.0 |
FLJ20647
| 6.2 |
KIAA0748
|
6.1 |
SUCLA2
| 6.0 |
N/A
| 6.1 |
N/A
| 6.3 |
CD40LG
|
6.1 |
C21orf7
| 6.0 |
LOC642376
| 6.1 |
CLDN1
| 6.3 |
PCDH10
|
6.2 |
TNPO1
| 6.0 |
MYOZ3
| 6.1 |
TRBV5-4
| 6.3 |
LOC644273
|
6.2 |
LOC643514
| 6.1 |
FLJ20647
| 6.1 |
CARD11
| 6.3 |
CD96
|
6.2 |
ALS2CR13
| 6.1 |
CD96
| 6.1 |
LOC441320
| 6.3 |
TRA@
|
6.2 |
CREB1
| 6.2 |
MAL
| 6.1 |
ACADSB
| 6.3 |
TRBV3-1
|
6.2 |
C17orf45
| 6.2 |
GIMAP5
| 6.1 |
NXPH4
| 6.4 |
TRA@
|
6.3 |
NELL2
| 6.2 |
CLDN1
| 6.2 |
SCNN1D
| 6.4 |
LOC642483
|
6.3 |
C6orf32
| 6.2 |
CD3D
| 6.2 |
MTMR1
| 6.5 |
ANKDD1A
|
6.3 |
LOC642455
| 6.2 |
LY9
| 6.2 |
MAL
| 6.5 |
N/A
|
6.4 |
GMDS
| 6.3 |
LOC123876
| 6.2 |
ZAP70
| 6.5 |
N/A
|
6.4 |
ABHD6
| 6.3 |
TNFRSF25
| 6.3 |
MAL
| 6.5 |
LY9
|
6.4 |
DAPP1
| 6.3 |
C21orf7
| 6.3 |
IL2RB
| 6.6 |
CD8B
|
6.4 |
SH3BGRL
| 6.3 |
LOC645885
| 6.3 |
EDG8
| 6.6 |
MGC26597
|
6.5 |
IL7R
| 6.3 |
BLOC1S3
| 6.3 |
HKDC1
| 6.7 |
TRBV19
|
6.6 |
LOC441601
| 6.3 |
LOC644727
| 6.3 |
SCAP1
| 6.7 |
LOC145783
|
6.6 |
GPR18
| 6.4 |
CCDC45
| 6.3 |
LOC440455
| 6.8 |
CD8B
|
6.7 |
P2RX5
| 6.4 |
C21orf7
| 6.3 |
CD300E
| 6.9 |
C21orf7
|
6.7 |
LY9
| 6.5 |
CD28
| 6.4 |
LY9
| 6.9 |
UBASH3A
|
6.8 |
GGPS1
| 6.5 |
LOC440455
| 6.4 |
KIR2DS2
| 7.0 |
LOC400768
|
6.8 |
EIF3S6
| 6.5 |
IL24
| 6.4 |
SLAMF6
| 7.1 |
CD8B
|
6.8 |
ARHGAP15
| 6.5 |
GHRL
| 6.4 |
SAA3P
| 7.1 |
HAND1
|
6.8 |
SF3B1
| 6.5 |
FAM113B
| 6.4 |
SF3A2
| 7.2 |
LOC126075
|
6.8 |
GPR89A
| 6.5 |
LOC644663
| 6.5 |
UNQ470
| 7.2 |
TNFRSF7
|
6.9 |
LOC129293
| 6.5 |
C15orf37
| 6.5 |
C6orf21
| 7.3 |
LEF1
|
6.9 |
CPNE3
| 6.5 |
MAL
| 6.6 |
CD96
| 7.3 |
HLA-DOA
|
6.9 |
LY9
| 6.5 |
LOC644445
| 6.6 |
CD244
| 7.4 |
LOC646279
|
7.0 |
PIP3-E
| 6.6 |
LOC126075
| 6.6 |
N/A
| 7.4 |
YLPM1
|
7.0 |
TAF9
| 6.6 |
1-Sep
| 6.6 |
KLRK1
| 7.4 |
LOC643514
|
7.0 |
N/A
| 6.6 |
UBASH3A
| 6.6 |
C16orf5
| 7.5 |
MTMR1
|
7.0 |
KIAA0748
| 6.7 |
SAA3P
| 6.6 |
TRBC1
| 7.6 |
NOG
|
7.1 |
CD55
| 6.8 |
CD6
| 6.6 |
LOC339778
| 7.7 |
TCF7
|
7.2 |
EIF3S6
| 6.8 |
TRBV5-4
| 6.7 |
GNLY
| 7.7 |
KIAA0748
|
7.2 |
PGRMC2
| 6.9 |
1-Sep
| 6.7 |
LDLRAP1
| 7.7 |
C21orf7
|
7.3 |
C21orf7
| 6.9 |
LOC129293
| 6.8 |
HAND1
| 7.7 |
PRDM9
|
7.4 |
PSMD6
| 7.0 |
SCNN1D
| 6.8 |
CD3D
| 7.7 |
FCER2
|
7.5 |
ABLIM1
| 7.0 |
SIT1
| 6.8 |
FLJ45825
| 7.9 |
CD8B
|
7.6 |
STAG2
| 7.1 |
GATA3
| 6.8 |
SF3A2
| 8.0 |
LEF1
|
7.8 |
CCDC45
| 7.1 |
CD7
| 6.8 |
CXCR3
| ||
7.8 |
UNQ470
| 7.1 |
CDKN3
| 6.8 |
KIR3DL3
| ||
7.9 |
LY9
| 7.2 |
SCAP1
| 6.8 |
LAT
| ||
8.0 |
CD40LG
| 7.3 |
TRA@
| 6.9 |
CD52
| ||
7.3 |
LY9
| 6.9 |
TNFRSF7
| ||||
7.3 |
DDAH1
| 6.9 |
LOC442726
| ||||
7.3 |
TRA@
| 6.9 |
3-Sep
| ||||
7.5 |
TNFRSF7
| 6.9 |
KIAA0748
| ||||
7.5 |
KIAA0748
| 6.9 |
XG
| ||||
7.6 |
ITM2A
| 6.9 |
KIAA1549
| ||||
7.6 |
CD5
| 7.0 |
RNF157
| ||||
7.6 |
D4S234E
| 7.0 |
SIT1
| ||||
7.6 |
CD300E
| 7.0 |
CD1C
| ||||
7.7 |
APBB1
| 7.0 |
SLC16A10
| ||||
7.8 |
CD3D
| 7.0 |
CD3G
| ||||
7.8 |
LCK
| 7.1 |
CD6
| ||||
7.8 |
UBASH3A
| 7.1 |
LY9
| ||||
7.9 |
XG
| 7.1 |
FLT3LG
| ||||
7.1 |
LOC647353
| ||||||
7.2 |
LOC123876
| ||||||
7.2 |
CX3CR1
| ||||||
7.2 |
LOC126075
| ||||||
7.3 |
NELL2
| ||||||
7.4 |
LY9
| ||||||
7.4 |
MAL
| ||||||
7.4 |
KIR2DS2
| ||||||
7.4 |
CHIA
| ||||||
7.4 |
BIN1
| ||||||
7.5 |
CCDC78
| ||||||
7.5 |
MAL
| ||||||
7.5 |
C21orf7
| ||||||
7.5 |
KIR2DL4
| ||||||
7.6 |
CD6
| ||||||
7.6 |
CD3D
| ||||||
7.7 |
1-Sep
| ||||||
7.7 |
LCK
| ||||||
7.8 |
ITM2A
| ||||||
7.8 |
TRA@
| ||||||
7.9 |
SIT1
| ||||||
7.9 |
CD5
| ||||||
8.0 |
CD8A
| ||||||
8.0 |
LOC129293
|
AE-1 vs Stable | AE-3 vs Stable | AE-10 vs Stable | |||
---|---|---|---|---|---|
Fold changes | Genes | Fold changes | Genes | Fold changes | Genes |
5.0 |
PRODH
| 10.2 |
KSP37
| 10.1 |
LOC646781
|
5.1 |
MT1F
| 10.3 |
DUB3
| 10.1 |
LOC389634
|
5.1 |
OR2A7
| 10.6 |
DUB3
| 10.1 |
LOC441056
|
5.3 |
CD8B
| 10.8 |
TCF7
| 10.1 |
LOC340243
|
5.4 |
CGI-38
| 11.2 |
CX3CR1
| 10.2 |
C1QL2
|
5.4 |
DMBT1
| 17.6 |
MGC35295
| 10.2 |
LOC653541
|
5.4 |
N/A
| 19.9 |
STAC2
| 10.2 |
LOC158318
|
5.4 |
GNLY
| 25.0 |
AZGP1
| 10.3 |
N/A
|
5.5 |
LCK
| 10.4 |
LOC644373
| ||
5.5 |
DZIP1
| 10.6 |
SPDEF
| ||
5.6 |
TCF7
| 10.7 |
DUX1
| ||
5.6 |
MGC45438
| 10.9 |
LOC643001
| ||
5.6 |
UNQ470
| 11.1 |
LOC391767
| ||
5.8 |
MGLL
| 11.2 |
LOC645509
| ||
5.8 |
B4GALNT3
| 11.7 |
FLJ36131
| ||
5.9 |
CGI-38
| 11.8 |
LOC441323
| ||
5.9 |
CGI-38
| 11.9 |
LOC440015
| ||
6.1 |
LOC388886
| 11.9 |
LOC441812
| ||
6.1 |
GNLY
| 12.0 |
TCEB3C
| ||
6.2 |
N/A
| 12.1 |
SPDEF
| ||
6.4 |
CD8B
| 12.3 |
DUX4
| ||
6.4 |
AEBP2
| 12.5 |
LOC285697
| ||
6.4 |
EDG8
| 12.9 |
LOC646066
| ||
6.5 |
PRDM16
| 13.3 |
LOC441873
| ||
6.8 |
CX3CR1
| 13.6 |
LOC645402
| ||
7.0 |
MGC45438
| 13.7 |
LOC285563
| ||
7.3 |
MST1
| 13.9 |
LOC391763
| ||
7.4 |
LOC644088
| 14.4 |
DUB3
| ||
7.5 |
EDG8
| 14.7 |
LOC391766
| ||
10.1 |
MGC45438
| 15.0 |
LOC392197
| ||
12.6 |
MGC35295
| 15.0 |
REXO1L2P
| ||
15.5 |
STAC2
| 15.2 |
DUB3
| ||
19.1 |
AZGP1
| 15.2 |
LOC402199
| ||
15.7 |
LOC653442
| ||||
15.8 |
LOC653455
| ||||
16.0 |
LOC402207
| ||||
16.5 |
LOC391745
| ||||
16.7 |
LOC392188
| ||||
18.1 |
REXO1L6P
| ||||
19.1 |
LOC391764
| ||||
19.4 |
DUB3
| ||||
20.6 |
LOC645836
| ||||
21.0 |
LOC391749
| ||||
23.8 |
LOC402110
| ||||
24.2 |
REXO1L7P
| ||||
29.6 |
REXO1L1
| ||||
30.0 |
STAC2
| ||||
33.5 |
REXO1L3P
| ||||
39.7 |
REXO1L5P
|
AE-3 vs AE-1 | AE-10 vs AE-1 | AE-10 vs AE-3 | |||
---|---|---|---|---|---|
Fold changes | Genes | Fold changes | Genes | Fold changes | Genes |
5.0 |
ITGB3
| 10.2 |
MPO
| 10.3 |
MOXD1
|
5.1 |
CGI-69
| 10.4 |
LOC653492
| 10.3 |
LOC152573
|
5.2 |
SPTB
| 10.5 |
SPP1
| 10.7 |
SPDEF
|
5.2 |
BCL2L1
| 10.6 |
ANK1
| 10.8 |
CCDC80
|
5.2 |
GATA1
| 11.0 |
DEFA4
| 11.0 |
CTSG
|
5.3 |
FBXO7
| 11.0 |
MOXD1
| 11.0 |
CAMP
|
5.6 |
SELENBP1
| 11.0 |
HIG2
| 11.3 |
PLA2G2D
|
5.8 |
OSBP2
| 11.1 |
OSBP2
| 11.4 |
SPP1
|
5.9 |
LOC643855
| 11.2 |
REXO1L3P
| 11.6 |
S100P
|
6.1 |
ERAF
| 11.6 |
SPDEF
| 11.7 |
SLC4A11
|
6.2 |
EPB49
| 12.0 |
COL1A1
| 11.8 |
COL3A1
|
6.2 |
MYH9
| 12.2 |
BPI
| 11.8 |
SPAG4
|
6.4 |
ALAS2
| 12.3 |
SNCA
| 12.5 |
THBS2
|
7.4 |
LOC644462
| 12.3 |
SLC4A11
| 12.7 |
MPO
|
7.8 |
GMPR
| 12.5 |
COL1A1
| 13.0 |
PRTN3
|
8.1 |
ANK1
| 12.6 |
AZU1
| 13.2 |
COL1A1
|
8.9 |
BPGM
| 12.6 |
ARG1
| 13.3 |
ELA2
|
9.1 |
FAM46C
| 13.2 |
GREM1
| 14.3 |
LIF
|
9.2 |
LOC643497
| 13.5 |
DEFA4
| 14.4 |
CEACAM5
|
9.4 |
TRIM58
| 13.5 |
ELA2
| 14.6 |
RNF183
|
9.4 |
MBNL3
| 14.2 |
CEACAM5
| 14.9 |
B3Gn-T6
|
9.5 |
EPB49
| 14.5 |
ITGA11
| 15.1 |
AZU1
|
9.6 |
EPB49
| 15.0 |
CEACAM8
| 15.4 |
ITGA11
|
9.6 |
EPB42
| 15.3 |
SPTB
| 15.9 |
DEFA4
|
9.7 |
EPB41
| 15.6 |
CEACAM5
| 16.4 |
CEACAM5
|
9.7 |
SLC14A1
| 16.6 |
LIF
| 17.5 |
MS4A3
|
9.9 |
EPB42
| 17.1 |
TRIM58
| 17.8 |
ARG1
|
10.1 |
SNCA
| 19.2 |
THY1
| 20.4 |
THY1
|
13.5 |
TRIM58
| 19.5 |
MS4A3
| 21.1 |
MS4A3
|
19.7 |
SLC4A1
| 23.1 |
TRIM58
| 22.5 |
SPP1
|
20.7 |
EPB41
| 24.1 |
MS4A3
| 34.4 |
SFRP2
|
21.6 |
CA1
| 27.1 |
SFRP2
| 49.9 |
PLUNC
|
29.9 |
EPB42
| 57.1 |
CALCA
| ||
30.4 |
SPP1
| 68.9 |
CALCA
| ||
41.9 |
ALAS2
| 80.4 |
BPIL1
| ||
43.8 |
EPB42
| 93.1 |
BPIL1
| ||
44.2 |
CALCA
| ||||
48.5 |
PLUNC
| ||||
55.5 |
SLC4A1
| ||||
58.6 |
CALCA
| ||||
70.0 |
BPIL1
| ||||
84.3 |
BPIL1
| ||||
109.9 |
CA1
|
COPD-specific genes
Fold change | >5 | >10 | ||||
---|---|---|---|---|---|---|
Upregulated | 79 | 14 | ||||
Downregulated | 23 | 2 | ||||
Unexpressed genes (>10) | ||||||
SEQ-ID | Gene name | Full name of gene | Stable vs Con | AE-1 vs Con | AE-3 vs Con | AE-10 vs Con |
D12502 |
CEACAM1
| Carcinoembryonic antigen-related cell adhesion molecule 1 | 10.1 | 83.0 | 66.5 | 10.5 |
NM_004369 |
COL6A3
| Collagen, type VI, α3 | 10.4 | 21.0 | 22.4 | 10.8 |
AF064599 |
NOL3
| Nucleolar protein 3 (apoptosis repressor with CARD domain) | 12.1 | 13.6 | 16.3 | 11.5 |
BC042586 |
COL1A2
| Collagen, type I, α2 | 13.1 | 72.3 | 92.9 | 17.2 |
BC014473 |
CEACAM1
| Carcinoembryonic antigen-related cell adhesion molecule 1 | 14.7 | 101.2 | 61.0 | 11.8 |
AY358857 |
MLPH
| Melanophilin | 17.0 | 10.3 | 12.8 | 12.2 |
AF348143 |
MUC1
| Mucin 1, cell surface-associated | 20.0 | 19.7 | 20.1 | 28.6 |
NM_012385 |
P8
| p8 protein (candidate of metastasis 1) | 20.1 | 19.1 | 21.3 | 22.1 |
BC093946 |
UNQ473
| DMC | 20.2 | 45.9 | 53.1 | 24.3 |
NM_001305 |
CLDN4
| Claudin 4 | 23.0 | 34.4 | 39.1 | 20.7 |
NM_002933 |
RNASE1
| Ribonuclease, RNase A family, 1 (pancreatic) | 26.9 | 12.5 | 15.2 | 37.2 |
BC053636 |
H19
| H19, imprinted maternally expressed untranslated mRNA | 29.5 | 37.2 | 28.0 | 11.8 |
BC069423 |
DEFA1
| Defensin, α1 | 33.0 | 96.1 | 86.7 | 10.2 |
XM_928349 |
LOC653600
| Similar to neutrophil defensin 1 precursor (HNP-1) (HP-1) (HP1) (defensin, α1) | 43.1 | 115.8 | 109.4 | 12.8 |
Downregulated genes (>5) | ||||||
SEQ-ID
|
Gene name
|
Full name of genes
|
Stable vs Con
|
AE-1 vs Con
|
AE-3 vs Con
|
AE-10 vs Con
|
M38056 |
HLA-DOA
| Major histocompatibility complex, class II, DOα | 5.3 | 5.9 | 5.6 | 7.3 |
AY209188 |
SAA3P
| Serum amyloid A3 pseudogene | 5.3 | 6.7 | 6.4 | 11.9 |
BC069511 |
UBASH3A
| Ubiquitin-associated and SH3 domain-containing, A | 5.5 | 10.4 | 14.3 | 6.9 |
AJ421515 |
CRTAC1
| Cartilage acidic protein 1 | 5.6 | 25.4 | 12.5 | 11.9 |
AL133666 |
EPHA6
| EPH receptor A6 | 5.6 | 5.8 | 8.2 | 5.3 |
NM_020152 |
C21orf7
| Chromosome 21 open reading frame 7 | 5.7 | 8.2 | 9.7 | 10.4 |
XM_089384 |
TTC24
| Tetratricopeptide repeat domain 24 | 5.8 | 11.7 | 12.5 | 12.7 |
NM_006850 |
IL24
| Interleukin 24 | 6.0 | 6.5 | 10.7 | 11.1 |
AL713701 |
C21orf7
| Chromosome 21 open reading frame 7 | 6.1 | 9.5 | 9.5 | 10.0 |
XM_931594 |
LOC643514
| Hypothetical protein LOC643514 | 6.2 | 11.4 | 5.7 | 7.4 |
NM_006159 |
NELL2
| NEL-like 2 (chicken) | 6.3 | 11.5 | 7.3 | 10.0 |
NM_002348 |
LY9
| Lymphocyte antigen 9 | 6.7 | 8.2 | 7.4 | 6.5 |
XM_934852 |
LOC129293
| Hypothetical protein LOC129293 | 6.9 | 14.5 | 12.9 | 9.4 |
BC062589 |
LY9
| Lymphocyte antigen 9 | 6.9 | 7.3 | 7.1 | 5.5 |
XM_934149 |
KIAA0748
| KIAA0748 | 7.0 | 7.5 | 11.2 | 6.2 |
BC008567 |
C21orf7
| Chromosome 21 open reading frame 7 | 7.3 | 6.3 | 7.5 | 7.7 |
NM_138363 |
CCDC45
| Coiled-coil domain containing 45 | 7.8 | 6.4 | 5.9 | 5.2 |
BC022101 |
UNQ470
| GAAI470 | 7.8 | 44.1 | 18.1 | 32.3 |
BC027920 |
LY9
| Lymphocyte antigen 9 | 7.9 | 6.2 | 5.8 | 5.3 |
BC033896 |
AK5
| Adenylate kinase 5 | 8.2 | 8.2 | 10.6 | 9.9 |
XM_085151 |
YLPM1
| YLP motif containing 1 | 10.7 | 8.7 | 5.1 | 7.4 |
NM_014553 |
TFCP2L1
| Transcription factor CP2-like 1 | 16.1 | 21.8 | 32.0 | 14.9 |
NM_001007098 |
SCP2
| Sterol carrier protein 2 | 21.0 | 27.9 | 18.7 | 18.6 |
AECOPD-specific genes
Fold change | >5 | >10 | |||||
---|---|---|---|---|---|---|---|
Upregulated | 58 | 8 | |||||
Fold change | >2 | >3 | |||||
Downregulated | 238 | 8 | |||||
Selected co–differentially upregulated genes (>10-fold) | |||||||
SEQ_ID | Gene name | AE-1 | AE-3 | AE-10 | |||
AE-1 vs Con | AE-1 vs Stable | AE-3 vs Con | AE-3 vs Stable | AE-10 vs Con | AE-10 vs Stable | ||
BC004490 |
FOS
| 27.4 | 28.6 | 33.5 | 34.9 | 13.2 | 13.7 |
BC015492 |
IFI27
| 12.3 | 10.3 | 13.1 | 11.0 | 21.6 | 18.1 |
NM_001554 |
CYR61
| 12.0 | 40.3 | 11.2 | 37.6 | 11.7 | 39.2 |
NM_001901 |
CTGF
| 35.7 | 26.6 | 36.9 | 27.5 | 59.3 | 44.2 |
NM_003979 |
GPRC5A
| 21.2 | 12.6 | 19.2 | 11.4 | 75.8 | 45.1 |
NM_006732 |
FOSB
| 21.7 | 13.7 | 40.1 | 25.3 | 35.6 | 22.5 |
NM_133504 |
DCN
| 19.0 | 17.2 | 19.6 | 17.8 | 20.0 | 18.1 |
XM_373497 |
LOC387763
| 41.4 | 13.5 | 46.4 | 15.2 | 41.3 | 13.5 |
Selected co–differentially downregulated genes (>3-fold) | |||||||
SEQ_ID
|
Gene names
|
AE-1
|
AE-3
|
AE-10
| |||
AE-1 vs Con
|
AE-1 vs Stable
|
AE-3 vs Con
|
AE-3 vs Stable
|
AE-10 vs Con
|
AE-10 vs Stable
| ||
AJ002102 |
KIR2DS2
| 3.7 | 3.8 | 7.4 | 7.6 | 4.2 | 4.4 |
BC022407 |
SH2D1B
| 3.0 | 3.7 | 4.8 | 5.9 | 3.1 | 3.8 |
BC066595 |
SH2D1B
| 3.6 | 3.2 | 9.9 | 8.9 | 3.6 | 3.2 |
BC100911 |
CD8B
| 11.2 | 4.4 | 16.0 | 6.3 | 7.9 | 3.1 |
NM_001004698 |
OR2W5
| 3.7 | 3.1 | 4.7 | 4.0 | 3.7 | 3.1 |
NM_004931 |
CD8B
| 10.3 | 5.3 | 11.5 | 5.9 | 6.6 | 3.4 |
NM_031950 |
KSP37
| 4.8 | 5.0 | 9.8 | 10.2 | 3.0 | 3.1 |
NM_201633 |
TCF7
| 15.6 | 5.6 | 30.4 | 10.8 | 8.9 | 3.2 |
Dynamic change in gene expression in patients with AECOPD
Down–down | Down–up | Up–down | Up–up | ||
---|---|---|---|---|---|
Total | 353 | 784 | 1,005 | 127 | |
>2-fold | 52 | 131 | 238 | 8 | |
>4-fold | 3 | 3 | 7 | 0 | |
>5-fold | 2 | 0 | 0 | 0 | |
Selected co–differentially expressed genes at the down–down pattern (>4-fold) | |||||
SEQ-ID | Gene name | Full name of gene | AE-3 vs AE-1 | AE-10 vs AE-3 | |
NM_000032 |
ALAS2
| Aminolevulinate, delta-, synthase 2 | 6.4 | 6.5 | |
BC099627 |
EPB42
| Erythrocyte membrane protein band 4.2 | 9.9 | 4.4 | |
BC027890 |
CA1
| Carbonic anhydrase I | 21.6 | 5.1 | |
Selected co–differentially expressed genes at the down–up pattern (>4-fold) | |||||
SEQ-ID | Gene name | Full name of gene | AE-3 vs AE-1 | AE-10 vs AE-3 | |
AK127453 | N/A | Homo sapiens cDNA FLJ45545 fis, clone BRTHA2034281. | 4.7 | 5.7 | |
NM_003944 |
SELENBP1
| Selenium-binding protein 1 | 5.6 | 4.1 | |
BC090921 |
MYH9
| Myosin, heavy chain 9, non-muscle | 6.2 | 4.1 | |
Selected co–differentially expressed genes at the up–down pattern (>4-fold) | |||||
SEQ-ID | Gene name | Full name of gene | AE-3 vs AE-1 | AE-10 vs AE-3 | |
NM_181717 |
HCG27
| HLA complex group 27 | 4.1 | 7.3 | |
NM_177551 |
GPR109A
| G protein-coupled receptor 109A | 4.3 | 7.5 | |
NM_006018 |
GPR109B
| G protein-coupled receptor 109B | 4.4 | 5.1 | |
AF249277 |
MTHFS
| 5,10-methenyltetrahydrofolate synthetase (5-formyltetrahydrofolate cyclo-ligase) | 4.6 | 5.3 | |
AY234180 |
BCL2A1
| BCL2-related protein A1 | 5.2 | 4.0 | |
BC010952 |
PI3
| Peptidase inhibitor 3, skin-derived (SKALP) | 6.0 | 4.4 | |
NM_002243 |
KCNJ15
| Potassium inwardly rectifying channel, subfamily J, member 15 | 7.0 | 4.8 | |
Selected co–differentially expressed genes at the up–up pattern (>2-fold) | |||||
SEQ-ID | Gene name | Full name of gene | AE-3 vs AE-1 | AE-10 vs AE-3 | |
Z15108 |
PRKCZ
| Protein kinase C, zeta | 2.0 | 2.8 | |
BC037798 |
CGI-38
| Brain-specific protein | 2.0 | 2.4 | |
NM_001033581 |
PRKCZ
| Protein kinase C, zeta | 2.1 | 2.8 | |
NM_007168 |
ABCA8
| ATP-binding cassette, subfamily A, member 8 | 2.1 | 4.0 | |
AK022468 |
SORBS1
| Sorbin and SH3 domain containing 1 | 2.3 | 3.5 | |
NM_006403 |
NEDD9
| Neural precursor cell expressed, developmentally downregulated 9 | 2.3 | 2.2 | |
NM_023037 |
FRY
| Furry homologue (Drosophila) | 2.3 | 2.1 | |
NM_016730 |
FOLR1
| Folate receptor 1 (adult) | 3.0 | 11.7 | |
Down–down | GENE_NAME | SEQ_ID | AE-1 vs Stable | AE-3 vs Stable | AE-10 vs Stable |
ALAS2
| NM_000032 | 17.64 | 2.76 | −2.37 | |
EPB42
| BC099627 | 10.02 | 1.01 | −4.37 | |
CA1
| BC027890 | 103.93 | 4.81 | −1.06 | |
Down–up | GENE_NAME | SEQ_ID | AE-1 vs Stable | AE-3 vs Stable | AE-10 vs Stable |
N/A | AK127453 | −1.69 | −7.90 | −1.38 | |
SELENBP1
| NM_003944 | 3.97 | −1.41 | 2.92 | |
MYH9
| BC090921 | −1.36 | −8.40 | −2.04 | |
Up–down | GENE_NAME | SEQ_ID | AE-1 vs Stable | AE-3 vs Stable | AE-10 vs Stable |
HCG27
| NM_181717 | 1.09 | 4.47 | −1.63 | |
GPR109A
| NM_177551 | 4.12 | 17.79 | 2.36 | |
GPR109B
| NM_006018 | 2.64 | 11.64 | 2.28 | |
MTHFS
| AF249277 | 4.51 | 20.75 | 3.95 | |
BCL2A1
| AY234180 | 2.38 | 12.45 | 3.11 | |
PI3
| BC010952 | 1.03 | 6.20 | 1.42 | |
KCNJ15
| NM_002243 | 2.25 | 15.78 | 3.26 | |
Up–up | GENE_NAME | SEQ_ID | AE-1 vs Stable | AE-3 vs Stable | AE-10 vs Stable |
PRKCZ
| Z15108 | −1.25 | 1.61 | 4.46 | |
CGI-38
| BC037798 | −5.87 | −2.86 | −1.18 | |
PRKCZ
| NM_001033581 | −1.61 | 1.30 | 3.64 | |
ABCA8
| NM_007168 | −1.27 | 1.68 | 6.69 | |
SORBS1
| AK022468 | 1.28 | 2.92 | 10.30 | |
NEDD9
| NM_006403 | 2.43 | 5.57 | 12.15 | |
FRY
| NM_023037 | −1.11 | 2.08 | 4.34 | |
FOLR1
| NM_016730 | −4.20 | −1.39 | 8.39 |
Gene ontology analysis and pathway analysis
Discussion
Conclusions
Key messages
-
Circulating dynamic biomarkers were identified for the specificity and severity of AECOPD.
-
A panel of 16 genes were selected as AECOPD-specific biomarkers.
-
This is an initial study designed to examine gene expression profiles of peripheral blood mononuclear cells and identify dynamic changes of AECOPD-specific biomarkers.