Table 1 Correlation between OS and clinicopathologic features of GC patients in TCGA cohort.
Variables
|
Events/total
|
MST (months)
|
HR (95% CI)
|
P-value
|
Age (years)
|
144/348
|
29
|
|
0.022
|
<60
|
36/108
|
60
|
1
|
|
≥60
|
108/240
|
26
|
1.55(1.06-2.27)
|
|
Missing
|
3
|
|
|
|
Gender
|
144/351
|
29
|
|
0.178
|
Male
|
100/226
|
29
|
1
|
|
Female
|
44/125
|
35
|
0.78(0.55-1.12)
|
|
Missing
|
0
|
|
|
|
Anatomic neoplasm
|
138/337
|
29
|
|
0.919
|
Gastroesophageal junction
|
36/84
|
26
|
1
|
|
Fundus gastric body
|
50/123
|
28
|
0.92(0.60-1.41)
|
|
Gastric antrum
|
52/130
|
35
|
0.94(0.61-1.43)
|
|
Missing
|
14
|
|
|
|
HP infection
|
66/161
|
43
|
|
0.304
|
Positive
|
6/18
|
58
|
1
|
|
Negative
|
60/143
|
43
|
1.55(0.67-3.61)
|
|
Missing
|
190
|
|
|
|
Histologic type
|
144/350
|
29
|
|
0.057
|
Intestinal
|
64/160
|
38
|
1
|
|
Diffuse type
|
24/61
|
60
|
1.00(0.63-1.60)
|
|
Signet ring type
|
8/11
|
13
|
2.52(1.20-5.25)
|
|
Other types
|
48/118
|
26
|
1.29(0.88-1.88)
|
|
Missing
|
1
|
|
|
|
Histologic grade
|
140/342
|
29
|
|
0.169
|
G1
|
2/9
|
NA
|
1
|
|
G2
|
48/127
|
43
|
1.67(0.41-6.86)
|
|
G3
|
90/206
|
26
|
2.22(0.55-9.01)
|
|
Missing
|
9
|
|
|
|
MSS1
|
144/350
|
29
|
|
0.225
|
MSI-H
|
99/240
|
28
|
1
|
|
MSI-L
|
22/51
|
29
|
1.26(0.79-2.01)
|
|
MMS
|
23/59
|
35
|
0.76(0.48-1.19)
|
|
Missing
|
1
|
|
|
|
Pathological M
|
138/336
|
29
|
|
0.012
|
M1
|
13/23
|
12
|
1
|
|
M0
|
125/313
|
35
|
0.49(0.28-0.86)
|
|
Missing
|
15
|
|
|
|
Pathological N
|
139/341
|
29
|
|
0.004
|
N0
|
28/103
|
60
|
1
|
|
N+
|
111/238
|
25
|
1.83(1.21-2.76)
|
|
Missing
|
10
|
|
|
|
Pathological T
|
140/347
|
31
|
|
0.009
|
T1/T2
|
28/91
|
70
|
1
|
|
T3/T4
|
112/256
|
26
|
1.73(1.14-2.63)
|
|
Missing
|
4
|
|
|
|
TNM stage
|
136/338
|
29
|
|
<0.001
|
Stage I
|
11/47
|
73
|
1
|
|
Stage II
|
34/109
|
56
|
1.61(0.81-3.18)
|
|
Stage III
|
69/147
|
26
|
2.44(1.29-4.61)
|
|
Stage IV
|
22/35
|
16
|
3.79(1.84-7.82)
|
|
Missing
|
13
|
|
|
|
Cancer status
|
121/324
|
37
|
|
<0.001
|
Tumor free
|
35/206
|
NA
|
1
|
|
With tumor
|
86/118
|
17
|
5.53(3.70-8.26)
|
|
Missing
|
27
|
|
|
|
Primary therapy outcome
|
114/303
|
38
|
|
<0.001
|
CR
|
55/209
|
73
|
1
|
|
PR
|
4/5
|
17
|
4.23(1.52-11.78)
|
|
SD
|
7/25
|
31
|
1.89(0.86-4.18)
|
|
PD
|
48/64
|
13
|
4.33(2.91-6.45)
|
|
Missing
|
47
|
|
|
|
Radiation therapy
|
135/328
|
31
|
|
0.001
|
Yes
|
19/62
|
NA
|
1
|
|
No
|
116/266
|
26
|
2.32(1.42-3.80)
|
|
Missing
|
23
|
|
|
|
Residual tumor
|
121/316
|
37
|
|
<0.001
|
R1
|
9/14
|
13
|
1
|
|
R2
|
12/14
|
9
|
1.88(0.95-3.73)
|
|
R0
|
100/288
|
47
|
7.19(3.88-13.34)
|
|
Missing
|
35
|
|
|
|
Targeted therapy
|
134/326
|
31
|
|
0.022
|
Yes
|
56/151
|
43
|
1
|
|
No
|
78/175
|
26
|
1.49(1.06-2.10)
|
|
Missing
|
25
|
|
|
|
Abbreviations: OS, overall survival; GC, gastric cancer; TCGA, The Cancer Genome Atlas; HR, hazard ratio; MST, median survival time; G1, highly differentiated; G2, moderately differentiated; G3, poorly differentiated; MSI-H, microsatellite instability-altitude; MSI-L, Microsatellite instability-altitude; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; R1, microscopic residual tumor; R2, macroscopic residual tumor; R0, no residual tumor.
Table 2 Prognostic values of ADAMTS genes expression in GC OS of TCGA cohort.
Gene
|
Events/total (n=351)
|
MST (months)
|
Crude HR
(95% CI)
|
Crude
P-value
|
Adjusted HR
(95% CI)
|
Adjusted P-valuea
|
ADAMTS1
|
|
|
|
|
|
|
Low
|
61/176
|
56
|
1
|
|
1
|
|
High
|
83/175
|
26
|
1.52(1.09-2.12)
|
0.013
|
1.39(0.91-2.11)
|
0.125
|
ADAMTS2
|
|
|
|
|
|
|
Low
|
64/176
|
47
|
1
|
|
1
|
|
High
|
80/175
|
26
|
1.38(0.99-1.92)
|
0.055
|
1.30(0.85-1.98)
|
0.226
|
ADAMTS3
|
|
|
|
|
|
|
Low
|
63/176
|
37
|
1
|
|
1
|
|
High
|
81/175
|
27
|
1.25(0.90-1.73)
|
0.19
|
1.36(0.88-2.09)
|
0.168
|
ADAMTS4
|
|
|
|
|
|
|
Low
|
63/176
|
43
|
1
|
|
1
|
|
High
|
81/175
|
28
|
1.21(0.87-1.68)
|
0.266
|
1.34(0.87-2.07)
|
0.189
|
ADAMTS5
|
|
|
|
|
|
|
Low
|
70/176
|
27
|
1
|
|
1
|
|
High
|
74/175
|
35
|
1.09(0.79-1.52)
|
0.599
|
0.84(0.54-1.31)
|
0.441
|
ADAMTS6
|
|
|
|
|
|
|
Low
|
59/176
|
56
|
1
|
|
1
|
|
High
|
85/175
|
21
|
1.80(1.29-2.51)
|
0.001
|
1.89(1.19-3.01)
|
0.007
|
ADAMTS7
|
|
|
|
|
|
|
Low
|
64/176
|
43
|
1
|
|
1
|
|
High
|
80/175
|
26
|
1.33(0.95-1.85)
|
0.095
|
1.41(0.91-2.18)
|
0.120
|
ADAMTS8
|
|
|
|
|
|
|
Low
|
67/176
|
37
|
1
|
|
1
|
|
High
|
77/175
|
28
|
1.15(0.83-1.60)
|
0.401
|
1.52(0.97-2.39)
|
0.067
|
Notes: a Adjusted for age, TNM stage, cancer status, primary therapy outcome, residual tumor, targeted molecular therapy and radiation therapy.
Abbreviations: HR, hazard ratio; MST, median survival time; OS, overall survival.
Table 3 Stratified analysis of ADAMTS6 gene expression in clinicopathologic features of GC cases.
Variables
|
Cases
|
HR (95% CI)
|
Log-rank P-value
|
Age (years)
|
348
|
|
|
<60
|
108
|
1.01(0.46-2.21)
|
0.102
|
≥60
|
240
|
1.94(1.25-3.01)
|
0.048
|
Gender
|
351
|
|
|
Male
|
226
|
1.66(1.05-2.62)
|
0.021
|
Female
|
125
|
2.26(1.14-4.50)
|
0.293
|
Anatomic neoplasm
|
|
|
|
Gastroesophageal
|
337
|
|
|
Junction
|
84
|
0.79(0.29-2.15)
|
0.501
|
Fundus gastric body
|
123
|
0.70(0.39-1.24)
|
0.001
|
Gastric antrum
|
130
|
1.97(1.01-3.85)
|
0.001
|
HP infection
|
161
|
|
|
Positive
|
18
|
3.61(0.22-59.81)
|
0.180
|
Negative
|
143
|
1.20(0.65-2.23)
|
0.005
|
Histologic type
|
350
|
|
|
Intestinal
|
160
|
2.53(1.43-4.46)
|
P<0.001
|
Diffuse type
|
61
|
0.67(0.28-1.59)
|
0.158
|
Signet ring type
|
11
|
0.64(0.02-26.22)
|
0.312
|
Other types
|
118
|
1.96(1.01-3.82)
|
0.005
|
Histologic grade
|
342
|
|
|
G1
|
9
|
NA
|
NA
|
G2
|
127
|
1.15(0.59-2.26)
|
0.006
|
G3
|
206
|
2.38(1.49-3.81)
|
P<0.001
|
MSS1
|
350
|
|
|
MSI-H
|
240
|
1.67(1.08-2.59)
|
P<0.001
|
MSI-L
|
51
|
2.15(0.81-5.73)
|
0.099
|
MMS
|
59
|
2.62(0.88-7.81)
|
0.005
|
Pathological M
|
336
|
|
|
M1
|
23
|
1.19(0.07-19.35)
|
0.870
|
M0
|
313
|
1.63(1.12-2.38)
|
P<0.001
|
Pathological N
|
139/341
|
|
|
N0
|
103
|
0.90(0.35-2.30)
|
0.005
|
N+
|
111/238
|
2.20(1.41-3.42)
|
P<0.001
|
Pathological T
|
347
|
|
|
T1/T2
|
91
|
0.60(0.24-1.51)
|
0.118
|
T3/T4
|
256
|
2.24(1.44-3.50)
|
P<0.001
|
Pathologic stage
|
136/338
|
|
|
Stage I
|
47
|
1.60(0.48-5.29)
|
0.402
|
Stage II
|
109
|
1.55(0.79-3.07)
|
0.478
|
Stage III
|
147
|
2.00(1.16-3.44)
|
0.039
|
Stage IV
|
35
|
3.11(0.70-13.86)
|
0.132
|
Cancer status
|
121/324
|
|
|
Tumor free
|
206
|
2.26(1.07-4.80)
|
P<0.001
|
With tumor
|
118
|
1.71(1.06-2.76)
|
0.108
|
Radiation therapy
|
135/328
|
|
|
Yes
|
62
|
2.26(0.80-6.39)
|
0.287
|
No
|
266
|
1.75(1.78-2.59)
|
P<0.001
|
Residual tumor
|
121/316
|
|
|
R1
|
14
|
NA
|
NA
|
R2
|
14
|
0.78(0.02-41.15)
|
0.531
|
R0
|
288
|
1.71(1.13-2.58)
|
0.090
|
Targeted therapy
|
134/326
|
|
|
Yes
|
151
|
1.36(0.77-2.39)
|
0.388
|
No
|
175
|
1.92(1.18-3.12)
|
P<0.001
|
Abbreviations: ADAMTS, A Disintegrin and Metalloproteinase with Thrombospondin motifs; GC, gastric cancer; TCGA, The Cancer Genome Atlas; HP, Helicobacter Pylori; HR, hazard ratio; MST, median survival time; OS, overall survival; G1, highly differentiated; G2, moderately differentiated; G3, poorly differentiated; MSI-H, microsatellite instability-altitude; MSI-L, Microsatellite instability-altitude; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; T, tumour; N, node; M, metastasis; R1, microscopic residual tumor; R2, macroscopic residual tumor; R0, no residual tumor; CI, confidence interval; NA, Not Applicable.
Table 4 Joint effects survival analysis of clinical factors and the ADAMTS6 expression with OS.
Group
|
ADAMTS6
|
Variables
|
Events/total
|
MST (months)
|
Crude HR
(95% CI)
|
Crude
P-value
|
Adjusted
HR (95% CI)
|
Adjusted
P-valuea
|
Histologic grade
|
|
|
|
|
|
|
|
A
|
Low expression
|
G1 + G2
|
27/74
|
56
|
1
|
|
1
|
|
B
|
Low expression
|
G3 + G4
|
32/98
|
47
|
1.005(0.602-1.680)
|
0.984
|
0.734(0.394-1.371)
|
0.332
|
C
|
High expression
|
G1 + G2
|
23/62
|
31
|
I.226(0.701-2.142)
|
0.475
|
1.171(0.600-2.286)
|
0.644
|
D
|
High expression
|
G3 + G4
|
58/108
|
18
|
2.045(1.291-3.237)
|
0.002
|
1.815(1.035-3.184)
|
0.038
|
Radiation therapy
|
|
|
|
|
|
|
|
a
|
Low expression
|
Yes
|
6/31
|
47
|
1
|
|
1
|
|
b
|
Low expression
|
No
|
47/131
|
58
|
3.104(1.321-7.2940
|
0.009
|
3.265(1.276-8.353)
|
0.014
|
c
|
High expression
|
Yes
|
13/31
|
20
|
2.821(1.071-7.432)
|
0.036
|
2.644(0.954-7.324)
|
0.062
|
d
|
High expression
|
No
|
69/135
|
31
|
5.665(2.434-13.188)
|
<0.001
|
5.917(2.349-14.900)
|
<0.001
|
Radical resection
|
|
|
|
|
|
|
|
I
|
Low expression
|
R0
|
44/155
|
70
|
1
|
|
1
|
|
II
|
Low expression
|
R1+R2
|
5/9
|
8
|
3.046(1.204-7.707)
|
0.019
|
3.308(0.931-11.751)
|
0.064
|
IV
|
High expression
|
R0
|
56/133
|
27
|
1.829(1.230-2.720)
|
0.003
|
2.055(1.349-3.129)
|
0.001
|
III
|
High expression
|
R1+R2
|
16/19
|
12
|
5.009(2.807-8.937)
|
<0.001
|
3.485(1.719-7.067)
|
0.001
|
Targeted molecular therapy
|
|
|
|
|
|
|
|
i
|
Low expression
|
Yes
|
22/74
|
70
|
1
|
|
1
|
|
ii
|
Low expression
|
No
|
31/89
|
47
|
1.400(0.810-2.420)
|
0.228
|
0.928(0.478-1.801)
|
0.825
|
iii
|
High expression
|
Yes
|
34/77
|
29
|
1.829(1.068_3.133)
|
0.028
|
1.626(0.891-2.966)
|
0.113
|
iv
|
High expression
|
No
|
47/86
|
18
|
3.002(1.802-5.001)
|
<0.001
|
2.030(1.087-3.793)
|
0.026
|
Stage
|
|
|
|
|
|
|
|
|
E
|
Low expression
|
I + II
|
24/89
|
56
|
1
|
|
1
|
|
F
|
Low expression
|
III+IV
|
34/84
|
47
|
1.398(0.829-2.358)
|
0.209
|
1.839(0.975-3.469)
|
0.06
|
G
|
High expression
|
I + II
|
21/67
|
60
|
1.214(0.675-2.181)
|
0.517
|
1.579(0.794-3.142)
|
0.193
|
H
|
High expression
|
III+IV
|
57/98
|
17
|
2.916(1.807-4.704)
|
<0.001
|
3.897(2.117-7.176)
|
<0.001
|
Notes: a Adjusted for histologic grade, radiation therapy, radical resection, targeted molecular therapy and stage.
Abbreviations: ADAMTS, A Disintegrin and Metalloproteinase with Thrombospondin motifs; GC, gastric cancer; HR, hazard ratio; MST, median survival time; OS, overall survival; CI, confidence interval.
Table 5 Survival analysis of ADAMTS gene mRNA expression in GC cases in KM plotter database.
Gene/ Affymetrix ID
|
Low / high expression cases
|
HR (95%CI)
|
P-value
|
ADAMTS1/222486_s_at
|
317/314
|
1.68 (1.35 − 2.09)
|
2.9e−06
|
ADAMTS2/226311_at
|
316/315
|
1.49 (1.2 − 1.85)
|
3e−04
|
ADAMTS3/214913_at
|
448/428
|
1.33 (1.12 − 1.58)
|
0.00091
|
ADAMTS4/214913_at
|
448/428
|
1.33 (1.12 − 1.58)
|
0.00091
|
ADAMTS5/235368_at
|
317/314
|
1.4 (1.12 − 1.74)
|
0.0024
|
ADAMTS6/237411_at
|
319/312
|
1.7 (1.37 − 2.12)
|
1.5e−06
|
ADAMTS7/228911_at
|
344/287
|
1.63 (1.32 − 2.03)
|
7.2e−06
|
ADAMTS8/235649_at
|
316/315
|
1.72 (1.38 − 2.13)
|
9.9e−07
|
Abbreviations: ADAMTS, A Disintegrin and Metalloproteinase with Thrombospondin motifs; GC, gastric cancer; HR, hazard ratio; KM, Kaplan–Meier; CI, confidence interval.
Table 6 Stratified analysis of ADAMTS gene mRNA in Lauren typing in Kaplan–Meier plotter.
Gene
|
Lauren typing
|
Low / high expression cases
|
HR (95%CI)
|
P-value
|
ADAMTS1
|
Intestinal
|
136/133
|
1.79 (1.23 − 2.59)
|
0.0019
|
|
Diffuse
|
120/120
|
1.3 (0.92 − 1.83)
|
0.13
|
|
Mixed
|
14/15
|
1.96 (0.6 − 6.37)
|
0.26
|
ADAMTS2
|
Intestinal
|
136/133
|
1.55 (1.08 − 2.23)
|
0.017
|
|
Diffuse
|
120/120
|
1.37 (0.97 − 1.94)
|
0.069
|
|
Mixed
|
14/15
|
0.9 (0.3 − 2.68)
|
0.85
|
ADAMTS3
|
Intestinal
|
162/158
|
1.55 (1.13 − 2.13)
|
0.0063
|
|
Diffuse
|
120/121
|
1.35 (0.96 − 1.9)
|
0.088
|
|
Mixed
|
16/16
|
2.72 (0.92 − 8.06)
|
0.061
|
ADAMTS4
|
Intestinal
|
162/158
|
1.55 (1.13 − 2.13)
|
0.0063
|
|
Diffuse
|
120/121
|
1.35 (0.96 − 1.9)
|
0.088
|
|
Mixed
|
16/16
|
2.72 (0.92 − 8.06)
|
0.061
|
ADAMTS5
|
Intestinal
|
134/135
|
1.23 (0.85 − 1.77)
|
0.27
|
|
Diffuse
|
120/120
|
1.54 (1.09 − 2.18)
|
0.013
|
|
Mixed
|
14/15
|
0.9 (0.3 − 2.68)
|
0.85
|
ADAMTS6
|
Intestinal
|
139/130
|
1.81 (1.26 − 2.62)
|
0.0013
|
|
Diffuse
|
121/119
|
1.3 (0.93 − 1.83)
|
0.13
|
|
Mixed
|
14/15
|
0.74 (0.25 − 2.24)
|
0.6
|
ADAMTS7
|
Intestinal
|
147/122
|
2.33 (1.61 − 3.38)
|
4.3e−06
|
|
Diffuse
|
133/107
|
1.4 (0.99 − 1.96)
|
0.054
|
|
Mixed
|
16/13
|
1.54 (0.51 − 4.58)
|
0.44
|
ADAMTS8
|
Intestinal
|
134/135
|
1.42 (0.99 − 2.05)
|
0.057
|
|
Diffuse
|
121/119
|
1.34 (0.95 − 1.89)
|
0.093
|
|
Mixed
|
14/15
|
2.21 (0.68 − 7.21)
|
0.18
|
Abbreviations: HR, hazard ratio; CI, confidence interval.
Table 7 Stratified analysis of ADAMTS gene mRNA in stage in Kaplan–Meier plotter database.
Gene
|
Stage
|
Low / high expression cases
|
HR (95%CI)
|
P-value
|
ADAMTS1
|
I
|
31/31
|
1.95 (0.6 − 6.4)
|
0.26
|
|
II
|
69/66
|
1.57 (0.83 − 2.97)
|
0.16
|
|
III
|
98/99
|
1.11 (0.77 − 1.62)
|
0.57
|
|
IV
|
70/70
|
1.52 (1.02 − 2.27)
|
0.036
|
ADAMTS2
|
I
|
31/31
|
0.26 (0.07 − 0.96)
|
0.03
|
|
II
|
68/67
|
0.62 (0.33 − 1.19)
|
0.15
|
|
III
|
98/99
|
1.56 (1.07 − 2.28)
|
0.02
|
|
IV
|
70/70
|
1.29 (0.87 − 1.91)
|
0.2
|
ADAMTS3
|
I
|
35/32
|
1.18 (0.43 − 3.23)
|
0.75
|
|
II
|
70/70
|
1.52 (0.83 − 2.76)
|
0.17
|
|
III
|
152/153
|
1.13 (0.85 − 1.5)
|
0.4
|
|
IV
|
74/74
|
1.46 (1 − 2.15)
|
0.051
|
ADAMTS4
|
I
|
35/32
|
1.18 (0.43 − 3.23)
|
0.75
|
|
II
|
70/70
|
1.52 (0.83 − 2.76)
|
0.17
|
|
III
|
152/153
|
1.13 (0.85 − 1.5)
|
0.4
|
|
IV
|
74/74
|
1.46 (1 − 2.15)
|
0.051
|
ADAMTS5
|
I
|
31/31
|
0.48 (0.16 − 1.49)
|
0.19
|
|
II
|
68/67
|
1.66 (0.86 − 3.18)
|
0.13
|
|
III
|
98/99
|
1.81 (1.24 − 2.64)
|
0.002
|
|
IV
|
71/69
|
1.51 (1.02 − 2.25)
|
0.04
|
ADAMTS6
|
I
|
32/30
|
0.41 (0.12 − 1.33)
|
0.12
|
|
II
|
68/67
|
1.4 (0.74 − 2.63)
|
0.29
|
|
III
|
98/99
|
1.36 (0.93 − 1.98)
|
0.11
|
|
IV
|
70/70
|
1.31 (0.88 − 1.95)
|
0.18
|
ADAMTS7
|
I
|
34/28
|
2.56 (0.77 − 8.56)
|
0.11
|
|
II
|
82/53
|
1.35 (0.71 − 2.57)
|
0.35
|
|
III
|
110/87
|
1.77 (1.21 − 2.57)
|
0.0026
|
|
IV
|
74/66
|
1.76 (1.18 − 2.63)
|
0.0047
|
ADAMTS8
|
I
|
31/31
|
1.87 (0.56 − 6.23)
|
0.3
|
|
II
|
68/67
|
1.52 (0.8 − 2.88)
|
0.19
|
|
III
|
98/99
|
1.2 (0.82 − 1.74)
|
0.34
|
|
IV
|
70/70
|
1.4 (0.94 − 2.09)
|
0.096
|
Abbreviations: HR, hazard ratio; CI, confidence interval.
Table 8 Stratified analysis of ADAMTS gene mRNA in degree of tumor differentiation in Kaplan–Meier plotter.
Gene
|
Differentiation
|
Low / high expression cases
|
HR (95%CI)
|
P-value
|
ADAMTS1
|
G1
|
2/3
|
1142066032.99 (0 − Inf)
|
0.41
|
|
G2
|
34/33
|
0.89 (0.46 − 1.7)
|
0.72
|
|
G3
|
60/61
|
0.87 (0.53 − 1.4)
|
0.55
|
ADAMTS2
|
G1
|
2/3
|
1142066039.57 (0 − Inf)
|
0.41
|
|
G2
|
34/33
|
1.31 (0.69 − 2.52)
|
0.41
|
|
G3
|
60/61
|
1.34 (0.82 − 2.18)
|
0.24
|
ADAMTS3
|
G1
|
16/16
|
1.52 (0.64 − 3.61)
|
0.34
|
|
G2
|
34/33
|
1.35 (0.71 − 2.59)
|
0.36
|
|
G3
|
82/83
|
1.23 (0.82 − 1.83)
|
0.32
|
ADAMTS4
|
G1
|
16/16
|
1.52 (0.64 − 3.61)
|
0.34
|
|
G2
|
34/33
|
1.35 (0.71 − 2.59)
|
0.36
|
|
G3
|
82/83
|
1.23 (0.82 − 1.83)
|
0.32
|
ADAMTS5
|
G1
|
2/3
|
1142066032.99 (0 − Inf)
|
0.41
|
|
G2
|
34/33
|
0.96 (0.5 − 1.84)
|
0.91
|
|
G3
|
60/61
|
1.16 (0.72 − 1.88)
|
0.54
|
ADAMTS6
|
G1
|
2/3
|
1142066039.57 (0 − Inf)
|
0.41
|
|
G2
|
36/31
|
1.49 (0.78 − 2.84)
|
0.23
|
|
G3
|
62/59
|
1.07 (0.66 − 1.73)
|
0.78
|
ADAMTS7
|
G1
|
2/3
|
1142066042.6 (0 − Inf)
|
0.41
|
|
G2
|
40/27
|
2.39 (1.24 − 4.59)
|
0.0074
|
|
G3
|
60/61
|
0.77 (0.48 − 1.26)
|
0.3
|
ADAMTS8
|
G1
|
2/3
|
1142066039.57 (0 − Inf)
|
0.41
|
|
G2
|
34/33
|
1.43 (0.75 − 2.74)
|
0.28
|
|
G3
|
60/61
|
1.1 (0.68 − 1.79)
|
0.69
|
Abbreviations: HR, hazard ratio; CI, confidence interval.
Table 9 Stratified analysis of ADAMTS genes mRNA in treatment method in Kaplan–Meier plotter.
Gene
|
Treatment method
|
Low / high expression cases
|
HR (95%CI)
|
P-value
|
ADAMTS1
|
Surgery
|
189/191
|
1.66 (1.24 − 2.22)
|
0.00065
|
|
5-FU
|
17/17
|
0.99 (0.4 − 2.47)
|
0.98
|
ADAMTS2
|
Surgery
|
192/188
|
1.32 (0.99 − 1.76)
|
0.061
|
|
5-FU
|
17/17
|
2.26 (0.89 − 5.76)
|
0.08
|
ADAMTS3
|
Surgery
|
194/186
|
1.54 (1.15 − 2.06)
|
0.0032
|
|
5-FU
|
77/76
|
0.88 (0.63 − 1.24)
|
0.47
|
ADAMTS4
|
Surgery
|
194/186
|
1.54 (1.15 − 2.06)
|
0.0032
|
|
5-FU
|
77/76
|
0.88 (0.63 − 1.24)
|
0.47
|
ADAMTS5
|
Surgery
|
190/190
|
1.28 (0.96 − 1.71)
|
0.096
|
|
5-FU
|
17/17
|
0.68 (0.27 − 1.71)
|
0.42
|
ADAMTS6
|
Surgery
|
190/190
|
1.75 (1.31 − 2.34)
|
0.00014
|
|
5-FU
|
17/17
|
2.04 (0.81 − 5.16)
|
0.12
|
ADAMTS7
|
Surgery
|
209/171
|
1.57 (1.17 − 2.09)
|
0.0021
|
|
5-FU
|
17/17
|
1 (0.4 − 2.47)
|
1
|
ADAMTS8
|
Surgery
|
190/190
|
1.48 (1.11 − 1.98)
|
0.0075
|
|
5-FU
|
17/17
|
2.25 (0.85 − 5.95)
|
0.094
|
Abbreviations: HR, hazard ratio; CI, confidence interval.
Table 10 Stratified analysis of ADAMTS gene mRNA in HER2 state in Kaplan–Meier Plotter database.
Gene
|
HER2 state
|
Low / high expression cases
|
HR (95%CI)
|
P-value
|
ADAMTS1
|
Negative
|
214/215
|
1.6 (1.23 − 2.1)
|
0.00049
|
|
Positive
|
101/101
|
1.94 (1.32 − 2.84)
|
0.00063
|
ADAMTS2
|
Negative
|
214/215
|
1.46 (1.12 − 1.91)
|
0.0049
|
|
Positive
|
101/101
|
1.59 (1.09 − 2.32)
|
0.015
|
ADAMTS3
|
Negative
|
266/266
|
1.49 (1.19 − 1.87)
|
0.00053
|
|
Positive
|
172/172
|
1.26 (0.97 − 1.63)
|
0.082
|
ADAMTS4
|
Negative
|
266/266
|
1.49 (1.19 − 1.87)
|
0.00053
|
|
Positive
|
172/172
|
1.26 (0.97 − 1.63)
|
0.082
|
ADAMTS5
|
Negative
|
216/213
|
1.44 (1.1 − 1.87)
|
0.0077
|
|
Positive
|
102/100
|
1.37 (0.94 − 1.99)
|
0.1
|
ADAMTS6
|
Negative
|
215/214
|
1.75 (1.33 − 2.29)
|
4.2e−05
|
|
Positive
|
101/101
|
1.59 (1.09 − 2.31)
|
0.015
|
ADAMTS7
|
Negative
|
225/204
|
1.85 (1.42 − 2.43)
|
4.6e−06
|
|
Positive
|
104/98
|
1.33 (0.92 − 1.93)
|
0.13
|
ADAMTS8
|
Negative
|
214/215
|
1.75 (1.34 − 2.29)
|
3.7e−05
|
|
Positive
|
101/101
|
1.64 (1.12 − 2.38)
|
0.0096
|
Abbreviations: HR, hazard ratio; CI, confidence interval.