Dove Medical Press Web viewBrain and CNS cancer Glioblastoma vs. Normal 0.002-1.742 5% 15827123 3...
9
Supplementary Figure 1. The flow diagram of this work. Supplementary Figure 2. Correlation between GKN2 and the pathological stage of LUAD, LUSC, and STAD patients (GEPIA).
Transcript of Dove Medical Press Web viewBrain and CNS cancer Glioblastoma vs. Normal 0.002-1.742 5% 15827123 3...
Supplementary Figure 1. The flow diagram of this work.
Supplementary Figure 2. Correlation between GKN2 and the pathological stage of LUAD, LUSC, and STAD patients (GEPIA).
Supplementary Figure 3. The comparison of tumor infiltration levels among LUAD, LUSC, and STAD with different somatic copy number alterations for GKN2 gene (TIMER).
Supplementary Figure 4. Scatterplots of correlation between GKN2 expression and the expression of gene markers of neutrophils in LUAD, LUSC and STAD (TIMER).
Supplementary Table 1. GKN2 expression in cancers vs. normal tissue in Oncomine database.
Number of analysis
Cancer
Cancer type
P-value
Fold change
Rank (%)
Reference (PMID)
1
Brain and CNS cancer
Glioblastoma vs. Normal
0.002
-1.742
5%
15827123
3
Breast cancer
Invasive Ductal Breast Carcinoma vs. Normal
5.44E-04
2.313
1%
17389037
Male Breast Carcinoma vs. Normal
6.43E-09
1.623
2%
TCGA
Invasive Breast Carcinoma Stroma vs. Normal
8.74E-20
4.520
2%
18438415
2
Colorectal cancer
Cecum Adenocarcinoma vs. Normal
7.83E-12
-1.675
5%
TCGA
Colon Mucinous Adenocarcinoma vs. Normal
2.89E-10
-1.520
6%
TCGA
2
Esophageal cancer
Barrett's Esophagus vs. Normal
4.02E-09
34.088
1%
16952561
Esophageal Adenocarcinoma vs. Normal
9.43E-08
4.357
9%
21152079
9
Gastric cancer
Diffuse Gastric Adenocarcinoma vs. Normal
5.94E-17
-120.513
1%
21447720
Gastric Intestinal Type Adenocarcinoma vs. Normal
1.41E-08
-40.953
1%
21447720
Gastric Mixed Adenocarcinoma vs. Normal
1.95E-04
-56.173
4%
21447720
Gastric Adenocarcinoma vs. Normal
7.00E-03
-95.530
5%
21447720
Gastric Intestinal Type Adenocarcinoma vs. Normal
8.45E-10
-26.909
1%
19081245
Gastric Mixed Adenocarcinoma vs. Normal
1.80E-05
-115.731
2%
19081245
Diffuse Gastric Adenocarcinoma vs. Normal
3.40E-02
-5.918
9%
19081245
Gastric Cancer vs. Normal
9.30E-08
-5.982
1%
20965966
Gastric Cancer vs. Normal
2.00E-03
-38.638
4%
21132402
9
Lung cancer
Small Cell Lung Carcinoma vs. Normal
1.26E-04
-7.711
1%
11707590
Large Cell Lung Carcinoma vs. Normal
2.66E-04
-10.756
1%
11707590
Lung Adenocarcinoma vs. Normal
1.60E-06
-9.244
2%
11707590
Squamous Cell Lung Carcinoma vs. Normal
9.16E-06
-11.407
3%
11707590
Lung Adenocarcinoma vs. Normal
2.44E-20
-7.211
1%
22080568
Lung Adenocarcinoma vs. Normal
5.05E-19
-12.892
1%
20421987
Large Cell Lung Carcinoma vs. Normal
1.18E-17
-32.501
1%
20421987
Squamous Cell Lung Carcinoma vs. Normal
2.47E-22
-26.436
2%
20421987
Lung Adenocarcinoma vs. Normal
1.42E-28
-11.326
2%
22613842
1
Myeloma
Monoclonal Gammopathy of Undetermined Significance vs. Normal
5.58E-06
-1.789
3%
17023574
1
Sacroma
Gastrointestinal Stromal Tumor vs. Normal
4.26E-20
-346.365
1%
21447720
Supplementary Table 2. Correlation of GKN2 mRNA expression and clinicopathological factors in lung cancer by Kaplan-Meier plotter database.
Groups
Variables
OS
(overall survival)
FP
(first progression)
PPS
(post-progression survival)
N
Hazard ratio
P-value
N
Hazard ratio
P-value
N
Hazard ratio
P-value
Gender
female
374
0.96 (0.69 − 1.35)
0.83
253
0.91 (0.58 − 1.43)
0.69
56
1.77 (0.84 − 3.75)
0.13
male
659
0.81 (0.66 − 0.99)
0.044
343
0.85 (0.61 − 1.19)
0.35
82
0.81 (0.47 − 1.38)
0.43
Smoking history
exclude those never smoked
300
0.85 (0.57 − 1.28)
0.45
297
0.95 (0.64 − 1.41)
0.8
96
0.91 (0.55 − 1.52)
0.73
only those never smoked
141
0.62 (0.27 − 1.39)
0.24
141
0.48 (0.26 − 0.92)
0.023
40
1.47 (0.61 − 3.56)
0.39
Histology
adenocarcinoma
672
0.99 (0.78 − 1.25)
0.91
443
0.69 (0.5 − 0.95)
0.023
115
1.19 (0.73 − 1.94)
0.49
squamous cell carcinoma
271
0.94 (0.69 − 1.28)
0.69
141
0.73 (0.44 − 1.23)
0.24
20
1.08 (0.38 − 3.03)
0.88
Stage
1
449
0.74 (0.54 − 1.01)
0.058
316
0.74 (0.48 − 1.16)
0.19
76
1.18 (0.65 − 2.16)
0.58
2
161
1.16 (0.74 − 1.83)
0.51
125
1.1 (0.65 − 1.88)
0.73
54
1.22 (0.62 − 2.4)
0.57
3
44
1.33 (0.67 − 2.65)
0.42
17
-
-
8
-
-
AJCC stage T
1
224
0.73 (0.49 − 1.08)
0.12
54
1.03 (0.28 − 3.85)
0.96
9
1.25 (0.21 − 7.53)
0.81
2
190
1.19 (0.82 − 1.74)
0.36
121
1.06 (0.58 − 1.96)
0.85
39
1.06 (0.58 − 1.96)
0.44
3
29
0.84 (0.38 − 1.9)
0.68
2
-
-
1
-
-
4
23
0.89 (0.38 − 2.07)
0.79
7
-
-
5
-
-
AJCC stage N
0
324
0.88 (0.64 − 1.2)
0.42
126
0.93 (0.47 − 1.87)
0.84
31
0.81 (0.36 − 1.8)
0.6
1
102
1.02 (0.62 − 1.67)
0.94
51
1.22 (0.49 − 3)
0.67
18
1.03 (0.31 − 3.42)
0.96
2
32
0.91 (0.44 − 1.89)
0.8
0
-
-
0
-
-
AJCC stage M
0
462
0.8 (0.62 − 1.02)
0.071
177
0.84 (0.48 − 1.46)
0.53
49
0.89 (0.46 − 1.71)
0.72
1
8
-
-
0
-
-
0
-
-
Treatment groups
only surgical margins negative
204
0.54 (0.26 − 1.13)
0.095
204
0.36 (0.2 − 0.64)
0.00032
56
1.99 (0.94 − 4.21)
0.068
chemotherapy (no)
21
2.38 (0.43 − 13.07)
0.3
21
3.55 (0.94 − 13.51)
0.047
9
0.69 (0.07 − 7.07)
0.75
chemotherapy (yes)
34
0.52 (0.16 − 1.66)
0.26
35
0.95 (0.36 − 2.49)
0.92
14
0.34 (0.08 − 1.43)
0.13
“-“ means the analysis cannot preformed due to the small number of samples.
Supplementary Table 3. Correlation of GKN2 mRNA expression and clinicopathological factors in gastric cancer by Kaplan-Meier plotter database.
Groups
Variables
OS
(overall survival)
FP
(first progression)
PPS
(post-progression survival)
N
Hazard ratio
P-value
N
Hazard ratio
P-value
N
Hazard ratio
P-value
Gender
female
187
0.82 (0.54 − 1.26)
0.37
179
0.94 (0.62 − 1.43)
0.79
127
0.65 (0.4 − 1.07)
0.088
male
349
0.71 (0.53 − 0.95)
0.02
341
0.69 (0.51 − 0.92)
0.011
256
0.67 (0.48 − 0.93)
0.017
Perforation
no
169
0.94 (0.63 − 1.4)
0.76
169
0.89 (0.61 − 1.3)
0.55
67
0.96 (0.57 − 1.64)
0.89
yes
4
-
-
4
-
-
2
-
-
HER2 status
negative
429
0.86 (0.66 − 1.12)
0.26
356
0.75 (0.56 − 1)
0.047
283
0.74 (0.53 − 1.03)
0.074
positive
202
0.78 (0.54 − 1.13)
0.19
166
0.73 (0.48 − 1.1)
0.14
101
0.53 (0.32 − 0.87)
0.011
Stage
1
62
1.64 (0.54 − 5.02)
0.38
60
1.67 (0.55 − 5.12)
0.36
31
1.24 (0.28 − 5.59)
0.77
2
135
0.81 (0.44 − 1.52)
0.52
131
1.03 (0.57 − 1.87)
0.93
105
0.75 (0.39 − 1.44)
0.38
3
197
0.59 (0.41 − 0.87)
0.0064
186
0.55 (0.38 − 0.8)
0.0015
142
0.6 (0.39 − 0.92)
0.018
4
140
0.89 (0.6 − 1.32)
0.56
141
0.88 (0.6 − 1.29)
0.52
104
0.93 (0.6 − 1.45)
0.75
Stage T
1
14
-
-
14
-
-
3
-
-
2
241
0.81 (0.53 − 1.24)
0.34
239
1 (0.66 − 1.51)
0.99
196
0.76 (0.48 − 1.18)
0.22
3
204
0.59 (0.42 − 0.84)
0.0028
204
0.65 (0.46 − 0.91)
0.011
150
0.62 (0.42 − 0.92)
0.016
4
38
1.08 (0.47 − 2.45)
0.86
39
0.77 (0.36 − 1.66)
0.51
29
1.38 (0.56 − 3.44)
0.48
Stage N
0
74
1.01 (0.44 − 2.29)
0.99
72
1.04 (0.46 − 2.37)
0.92
41
0.79 (0.25 − 2.45)
0.68
1+2+3
422
0.64 (0.49 − 0.84)
0.00091
423
0.69 (0.53 − 0.88)
0.0034
337
0.65 (0.49 − 0.87)
0.0033
1
225
0.57 (0.38 − 0.87)
0.0079
222
0.64 (0.43 − 0.96)
0.027
169
0.56 (0.35 − 0.88)
0.011
2
121
0.6 (0.38 − 0.94)
0.025
125
0.68 (0.44 − 1.04)
0.076
105
0.65 (0.41 − 1.05)
0.077
3
76
0.71 (0.42 − 1.21)
0.2
76
0.65 (0.38 − 1.1)
0.11
63
0.86 (0.49 − 1.53)
0.61
Stage M
0
444
0.58 (0.44 − 0.77)
0.00013
443
0.66 (0.51 − 0.86)
0.0022
342
0.64 (0.47 − 0.86)
0.0032
1
56
1.47 (0.81 − 2.68)
0.21
56
2.09 (1.14 − 3.83)
0.016
36
0.56 (0.27 − 1.17)
0.12
Lauren classification
instestinal
269
0.76 (0.53 − 1.08)
0.13
263
0.77 (0.54 − 1.1)
0.15
192
0.69 (0.46 − 1.05)
0.08
diffuse
240
0.65 (0.46 − 0.92)
0.014
231
0.72 (0.51 − 1.01)
0.059
176
0.57 (0.39 − 0.84)
0.004
mixed
29
3.34 (1 − 11.2)
0.039
28
4.31 (1.44 − 12.87)
0.0047
16
-
-
Differentiation
poorly differentiated
121
0.64 (0.39 − 1.04)
0.067
121
0.6 (0.38 − 0.96)
0.029
49
1.12 (0.59 − 2.13)
0.72
moderately differentiated
67
1.78 (0.92 − 3.43)
0.082
67
1.49 (0.8 − 2.79)
0.2
24
1.52 (0.62 − 3.74)
0.36
well differentiated
5
-
-
5
-
-
0
-
-
Treatment
surgery alone
380
0.81 (0.61 − 1.08)
0.16
375
0.9 (0.69 − 1.19)
0.48
277
0.74 (0.55 − 1.02)
0.062
5 FU based adjuvant
34
0.2 (0.07 − 0.58)
0.0014
34
0.15 (0.05 − 0.44)
0.00011
21
1.29 (0.47 − 3.49)
0.62
other adjuvant
76
0.22 (0.07 − 0.66)
0.0029
64
0.42 (0.18 − 0.97)
0.037
74
0.31 (0.1 − 0.94)
0.029
“-“ means the analysis cannot preformed due to the small number of samples.
Supplementary Table 4. The cox proportional hazard model of GKN2 and six tumor-infiltrating immune cells in LUAD, LUSC and STAD (TIMER).
Surv(LUAD)
coef
HR
95%CI_l
95%CI_u
p.value
sig
B_cell
-5.305
0.005
0
0.064
0
***
CD8_Tcell
0.501
1.65
0.276
9.865
0.583
CD4_Tcell
2.741
15.498
1.103
217.8
0.042
*
Macrophage
0.118
1.125
0.086
14.776
0.929
Neutrophil
-0.799
0.45
0.01
20.441
0.682
Dendritic
-0.202
0.817
0.219
3.056
0.764
GKN2
-0.038
0.963
0.905
1.024
0.224
Surv(LUSC)
coef
HR
95%CI_l
95%CI_u
p.value
sig
B_cell
0.576
1.779
0.167
18.99
0.633
CD8_Tcell
-1.097
0.334
0.061
1.837
0.207
CD4_Tcell
0.286
1.331
0.122
14.508
0.815
Macrophage
-1.752
0.173
0.014
2.194
0.176
Neutrophil
1.136
3.113
0.135
71.937
0.478
Dendritic
0.545
1.725
0.434
6.864
0.439
GKN2
0.155
1.167
1.036
1.315
0.011
*
Surv(STAD)
coef
HR
95%CI_l
95%CI_u
p.value
sig
B_cell
3.185
24.161
0.35
1666.668
0.14
CD8_Tcell
-2.042
0.13
0.009
1.968
0.141
CD4_Tcell
-3.808
0.022
0
1.798
0.089
Macrophage
5.688
295.388
16.065
5431.245
0
***
Neutrophil
-0.666
0.514
0.003
87.457
0.799
Dendritic
1.496
4.464
0.394
50.536
0.227
GKN2
0.004
1.004
0.952
1.059
0.874
*P < 0.05; **P < 0.01; ***P < 0.001.
Supplementary Table 5. Correlation analysis between GKN2 and immune relate genes of monocytes and macrophages in LUAD, LUSC and STAD (GEPIA).
Description
Gene markers
LUAD
LUSC
STAD
Tumor
Tumor
Tumor
R
P-value
R
P-value
R
P-value
Neutrophils
MPO
−0.028
0.54
0.29
***
0.1
*
PTPRC
(CD45R)
0.13
**
0.29
***
0.2
***
FUT4 (CD15)
-0.055
0.23
0.032
0.48
0.053
0.28
Monocytes
CD14
−0.038
0.4
0.22
***
0.0072
0.88
CD36
0.41
***
0.45
***
0.18
**
ITGAM (CD11B）
0.019
0.67
0.24
***
0.12
*
TAMs
(tumor-associated macrophages)
CD68
0.1
*
0.27
***
0.1
*
CCL2
0.018
0.69
0.23
***
0.011
0.82
CSF1R
0.013
0.77
0.29
***
0.1
*
M1 macrophages
NOS2 (NOS2A)
0.14
**
0.084
0.063
−0.0057
0.91
CXCL10
−0.19
***
0.0084
0.85
−0.058
0.24
TNF
−0.047
0.3
0.11
*
0.13
**
M2 macrophages
CCL18
0.3
***
0.43
***
0.018
0.72
CD163
0.093
*
0.37
***
−0.041
0.41
IL10 (CSIF)
0.11
*
0.3
***
0.053
0.29
Tumor, correlation analysis in tumor tissue of TCGA.
R, p-value from Spearman's test. *P < 0.05; **P < 0.01; ***P < 0.001.
