01.12.2017 | Research article | Ausgabe 1/2017 Open Access

The important role of circulating CYFRA21-1 in metastasis diagnosis and prognostic value compared with carcinoembryonic antigen and neuron-specific enolase in lung cancer patients
- Zeitschrift:
- BMC Cancer > Ausgabe 1/2017
Electronic supplementary material
Background
Methods
Patients
Study design
Statistical methods
Results
Increased levels of CYFRA21-1 significantly correlated with metastatic disease
No. (%)
|
|||||
---|---|---|---|---|---|
Neg
|
Moderate
|
High
|
Total
|
P Value
|
|
1–3 fold
|
>3 fold
|
||||
(
n = 115)
|
(
n = 190)
|
(
n = 127)
|
(
n = 432)
|
||
Basic Characteristics
|
|||||
Age
|
|||||
< 45
|
5 (4.3)
|
16 (8.4)
|
7 (5.5)
|
28
|
0.101
|
45–60
|
58 (50.4)
|
72 (37.9)
|
46 (36.2)
|
176
|
|
> 60
|
52 (45.3)
|
102 (53.7)
|
74 (58.3)
|
228
|
|
Sex
|
|||||
Male
|
79 (68.7)
|
134 (70.5)
|
83 (65.4)
|
296
|
0.623
|
Female
|
36 (31.3)
|
56 (29.5)
|
44 (34.6)
|
136
|
|
Histological classification
|
|||||
SCC
|
21 (18.3)
|
42 (22.1)
|
56 (44.1)
|
119
|
|
ADC
|
64 (55.7)
|
103 (54.2)
|
58 (45.7)
|
225
|
<0.001**
|
SCLC
|
22 (19.1)
|
34 (17.9)
|
7 (5.5)
|
63
|
|
Others
|
8 (6.9)
|
11 (5.8)
|
6 (4.7)
|
25
|
|
Stages
|
|||||
I
|
12 (10.4)
|
6 (3.2)
|
0 (0.0)
|
18
|
<0.001**
|
II
|
7 (6.1)
|
8 (4.2)
|
2 (1.6)
|
17
|
|
III
|
40 (34.8)
|
50 (26.3)
|
38 (29.9)
|
128
|
|
IV
|
49 (42.6)
|
115 (60.5)
|
79 (62.2)
|
243
|
|
#Un.
|
7 (6.1)
|
11 (5.8)
|
8 (6.3)
|
26
|
|
Smoke status
|
|||||
No
|
55 (47.8)
|
80 (42.1)
|
56 (44.1)
|
191
|
0.621
|
Yes
|
60 (52.2)
|
110 (57.9)
|
71 (55.9)
|
241
|
|
Metastasis
|
|||||
Brain
|
|||||
No
|
104 (90.4)
|
162 (85.3)
|
105 (82.7)
|
371
|
0.212
|
Yes
|
11 (9.6)
|
28 (14.7)
|
22 (17.3)
|
61
|
|
Bone
|
|||||
No
|
101 (90.4)
|
142 (74.7)
|
92 (72.4)
|
335
|
<0.01**
|
Yes
|
14 (9.6)
|
48 (25.3)
|
35 (27.6)
|
97
|
|
Liver
|
|||||
No
|
113 (98.3)
|
170 (89.5)
|
108 (85.0)
|
391
|
<0.01**
|
Yes
|
2 (1.7)
|
20 (10.5)
|
19 (15.0)
|
41
|
|
Adrenal gland
|
|||||
No
|
113 (98.3)
|
173 (91.1)
|
119 (93.7)
|
405
|
<0.05*
|
Yes
|
2 (1.7)
|
17 (8.9)
|
8 (6.3)
|
27
|
|
Lymph node
|
|||||
No
|
66 (57.4)
|
68 (35.8)
|
37 (29.1)
|
171
|
<0.001***
|
Yes
|
49 (42.6)
|
122 (64.2)
|
90 (70.9)
|
261
|
|
Intrapulmonary
|
|||||
No
|
105 (91.3)
|
163 (85.8)
|
111 (87.4)
|
379
|
0.360
|
Yes
|
21 (9.1)
|
58 (14.9)
|
35 (14.2)
|
53
|
|
Pleural
|
|||||
No
|
100 (87.0)
|
170 (89.5)
|
98 (77.2)
|
368
|
<0.01**
|
Yes
|
15 (13.0)
|
20 (10.5)
|
29 (22.8)
|
64
|
|
Mediastinal
|
|||||
No
|
113 (98.3)
|
185 (97.4)
|
120 (94.5)
|
418
|
0.208
|
Yes
|
2 (1.7)
|
5 (2.6)
|
7 (5.5)
|
14
|
|
Peritoneum
|
|||||
No
|
115 (100)
|
178 (93.7)
|
116 (91.3)
|
409
|
<0.01**
|
Yes
|
0 (0.0)
|
12 (6.3)
|
11 (8.7)
|
23
|
|
Validation group
|
|||||
No. (%)
|
|||||
Neg
|
Moderate
|
High
|
Total
|
P Value
|
|
1–3 fold
|
>3 fold
|
||||
(
n = 116)
|
(
n = 200)
|
(
n = 120)
|
(
n = 436)
|
||
Basic Characteristics
|
|||||
Age
|
|||||
8 (6.9)
|
13 (6.5)
|
10 (8.3)
|
31
|
0.073
|
|
52 (44.8)
|
61 (30.5)
|
36 (30.0)
|
149
|
||
56 (48.3)
|
126 (63.0)
|
74 (61.7)
|
256
|
||
Sex
|
|||||
74 (63.8)
|
139 (69.5)
|
94 (78.3)
|
307
|
<0.05*
|
|
42 (36.2)
|
61 (30.5)
|
26 (21.7)
|
129
|
||
Histological classification
|
|||||
15 (12.9)
|
43 (21.5)
|
38 (31.7)
|
96
|
<0.001**
|
|
56 (48.3)
|
98 (49.0)
|
66 (55.0)
|
220
|
||
40 (34.5)
|
47 (23.5)
|
9 (7.5)
|
96
|
||
5 (4.3)
|
12 (6.0)
|
7 (5.8)
|
24
|
||
Stages
|
|||||
9 (7.8)
|
9 (4.5)
|
4 (3.3)
|
22
|
<0.05*
|
|
15 (12.9)
|
20 (10.0)
|
3 (2.5)
|
38
|
||
23 (19.8)
|
43 (21.5)
|
23 (19.2)
|
89
|
||
61 (52.6)
|
115 (57.5)
|
86 (71.7)
|
262
|
||
8 (6.9)
|
13 (6.5)
|
4 (3.3)
|
25
|
||
Smoke status
|
|||||
63 (54.3)
|
86 (43.0)
|
42 (35.0)
|
191
|
<0.05*
|
|
53 (45.7)
|
114 (57.0)
|
78 (65.0)
|
245
|
||
Metastasis
|
|||||
Brain
|
|||||
102 (87.9)
|
183 (91.5)
|
93 (77.5)
|
378
|
<0.01**
|
|
14 (12.1)
|
17 (8.5)
|
27 (22.5)
|
58
|
||
Bone
|
|||||
101 (87.1)
|
160 (80.0)
|
79 (65.8)
|
340
|
<0.001***
|
|
15 (12.9)
|
40 (20.0)
|
41 (34.2)
|
96
|
||
Liver
|
|||||
110 (94.8)
|
177 (88.5)
|
96 (80.0)
|
383
|
<0.01**
|
|
6 (5.2)
|
23 (11.5)
|
24 (20.0)
|
53
|
||
Adrenal gland
|
|||||
107 (92.2)
|
192 (96.0)
|
110 (91.7)
|
409
|
0.213
|
|
9 (7.8)
|
8 (4.0)
|
10 (8.3)
|
27
|
||
Lymph node
|
|||||
58 (50.0)
|
68 (34.0)
|
41 (34.2)
|
167
|
<0.01**
|
|
58 (50.0)
|
132 (66.0)
|
79 (65.8)
|
269
|
||
Intrapulmonary
|
|||||
105 (90.5)
|
169 (84.5)
|
101 (84.2)
|
375
|
0.262
|
|
11 (9.5)
|
31 (15.5)
|
19 (15.8)
|
61
|
||
Pleural
|
|||||
107 (92.2)
|
168 (81.5)
|
95 (79.2)
|
365
|
<0.05*
|
|
9 (7.8)
|
37 (18.5)
|
25 (20.8)
|
71
|
||
Mediastinal
|
|||||
114 (98.3)
|
192 (96.0)
|
112 (93.3)
|
418
|
0.161
|
|
2 (1.7)
|
8 (4.0)
|
8 (6.7)
|
18
|
||
Peritoneum
|
|||||
111 (95.7)
|
189 (94.5)
|
99 (82.5)
|
399
|
<0.01**
|
|
5 (4.3)
|
11 (5.5)
|
21 (17.5)
|
37
|
Correlation of CYFRA21-1 and NSE with metastases in ADC and SCC, respectively
No. (%)
|
|||||
---|---|---|---|---|---|
Neg
|
Moderate
|
High
|
Total
|
P Value
|
|
(1–3 fold)
|
>3 fold
|
||||
(
n = 120)
|
(
n = 201)
|
(
n = 124)
|
(
n = 445)
|
||
Basic Characteristics
|
|||||
Age
|
|||||
< 45 years
|
5 (4.2)
|
22 (11.0)
|
14 (11.3)
|
41
|
<0.05*
|
45–60 years
|
57 (47.5)
|
66 (32.8)
|
38 (30.6)
|
161
|
|
> 60 years
|
58 (48.3)
|
113 (56.2)
|
72 (58.1)
|
243
|
|
Sex
|
|||||
Male
|
65 (54.2)
|
112 (55.7)
|
71 (57.3)
|
248
|
0.889
|
Female
|
55 (45.8)
|
89 (44.3)
|
53 (42.7)
|
197
|
|
Stages
|
|||||
I + II
|
24 (20.0)
|
14 (7.0)
|
5 (4.0)
|
43
|
<0.001**
|
III + IV
|
91 (75.8)
|
181 (90.0)
|
116 (93.6)
|
388
|
|
Unknown
|
4 (4.2)
|
6 (3.0)
|
3 (2.4)
|
14
|
|
Smoke status
|
|||||
No
|
79 (65.9)
|
119 (59.2)
|
68 (54.8)
|
266
|
0.208
|
Yes
|
41 (34.1)
|
82 (40.8)
|
56 (45.2)
|
179
|
|
Metastasis
|
|||||
Brain
|
|||||
No
|
107 (89.2)
|
164 (81.6)
|
95 (76.6)
|
366
|
<0.05*
|
Yes
|
13 (10.8)
|
37 (18.4)
|
29 (23.4)
|
79
|
|
Bone
|
|||||
No
|
102 (85.0)
|
141 (70.1)
|
75 (60.5)
|
318
|
<0.001**
|
Yes
|
18 (15.0)
|
60 (29.9)
|
49 (39.5)
|
127
|
|
Liver
|
|||||
No
|
116 (96.7)
|
181 (90.1)
|
102 (82.3)
|
399
|
<0.05*
|
Yes
|
4 (3.3)
|
20 (9.9)
|
22 (17.7)
|
46
|
|
Adrenal gland
|
|||||
No
|
115 (95.8)
|
191 (95.0)
|
116 (93.5)
|
422
|
0.713
|
Yes
|
5 (4.2)
|
10 (5.0)
|
8 (6.5)
|
23
|
|
Lymph node
|
|||||
No
|
69 (57.5)
|
69 (34.3)
|
45 (36.3)
|
183
|
<0.001**
|
Yes
|
51 (42.5)
|
132 (65.7)
|
79 (63.7)
|
262
|
|
Intrapulmonary
|
|||||
No
|
111 (92.5)
|
165 (82.1)
|
105 (84.7)
|
381
|
<0.05*
|
Yes
|
9 (7.5)
|
36 (17.9)
|
19 (15.3)
|
64
|
|
Pleural
|
|||||
No
|
103 (85.8)
|
161 (80.1)
|
88 (71.0)
|
352
|
<0.05*
|
Yes
|
17 (14.2)
|
40 (19.9)
|
36 (29.0)
|
93
|
|
Mediastinal
|
|||||
No
|
119 (99.2)
|
195 (97.0)
|
118 (95.2)
|
432
|
0.178
|
Yes
|
1 (0.8)
|
6 (3.0)
|
6 (4.8)
|
13
|
|
Peritoneum
|
|||||
No
|
119 (99.2)
|
186 (92.5)
|
107 (86.3)
|
412
|
<0.05*
|
Yes
|
1 (0.8)
|
15 (7.5)
|
17 (13.7)
|
33
|
No. (%)
|
|||||
---|---|---|---|---|---|
Neg
|
Moderate
|
High
|
Total
|
P Value
|
|
(1–2 fold)
|
>2 fold
|
||||
(
n = 110)
|
(
n = 70)
|
(
n = 35)
|
(
n = 215)
|
||
Basic Characteristics
|
|||||
Age
|
|||||
< 45 years
|
3 (2.7)
|
2 (2.9)
|
0 (0.0)
|
5
|
0.622
|
45–60 years
|
40 (36.4)
|
23 (32.8)
|
9 (25.7)
|
72
|
|
> 60 years
|
67 (60.9)
|
45 (64.3)
|
26 (74.3)
|
138
|
|
Sex
|
|||||
Male
|
101 (91.8)
|
61 (87.1)
|
30 (85.7)
|
192
|
0.463
|
Female
|
9 (8.2)
|
9 (12.9)
|
5 (14.3)
|
23
|
|
Stages
|
|||||
I + II
|
26 (23.6)
|
6 (8.6)
|
1 (2.8)
|
33
|
<0.05*
|
III + IV
|
80 (72.7)
|
62 (88.6)
|
33 (94.4)
|
175
|
|
Unknown
|
4 (3.7)
|
2 (2.8)
|
1 (2.8)
|
7
|
|
Smoke status
|
|||||
No
|
22 (20.0)
|
16 (22.9)
|
9 (25.7)
|
47
|
0.753
|
Yes
|
88 (80.0)
|
54 (77.1)
|
26 (74.3)
|
168
|
|
Metastasis
|
|||||
Brain
|
|||||
No
|
107 (97.3)
|
62 (88.6)
|
27 (77.1)
|
196
|
<0.05*
|
Yes
|
3 (2.7)
|
8 (11.4)
|
8 (22.9)
|
19
|
|
Bone
|
|||||
No
|
100 (90.9)
|
55 (78.6)
|
27 (77.1)
|
182
|
<0.05*
|
Yes
|
10 (9.1)
|
15 (21.4)
|
8 (22.9)
|
33
|
|
Liver
|
|||||
No
|
102 (92.7)
|
61 (87.1)
|
27 (77.1)
|
190
|
0.062
|
Yes
|
8 (7.3)
|
9 (12.9)
|
8 (22.9)
|
25
|
|
Adrenal gland
|
|||||
No
|
106 (96.4)
|
64 (91.4)
|
32 (91.4)
|
202
|
0.316
|
Yes
|
4 (3.6)
|
6 (8.6)
|
3 (8.6)
|
13
|
|
Lymph node
|
|||||
No
|
51 (46.4)
|
19 (27.1)
|
9 (25.7)
|
79
|
<0.05*
|
Yes
|
59 (53.6)
|
51 (72.9)
|
26 (74.3)
|
136
|
|
Intrapulmonary
|
|||||
No
|
96 (87.3)
|
58 (82.9)
|
31 (88.6)
|
185
|
0.632
|
Yes
|
14 (12.7)
|
12 (17.1)
|
4 (11.4)
|
30
|
|
Pleural
|
|||||
No
|
98 (89.1)
|
59 (84.3)
|
31 (88.6)
|
188
|
0.622
|
Yes
|
12 (10.9)
|
11 (15.7)
|
4 (11.4)
|
27
|
|
Mediastinal
|
|||||
No
|
108 (98.2)
|
61 (87.1)
|
34 (97.1)
|
203
|
<0.05*
|
Yes
|
2 (1.8)
|
9 (12.9)
|
1 (2.9)
|
12
|
|
Peritoneum
|
|||||
No
|
109 (99.1)
|
61 (87.1)
|
31 (88.6)
|
201
|
<0.05*
|
Yes
|
1 (0.9)
|
9 (12.9)
|
4 (11.4)
|
14
|
Increased positive numbers of biomarkers as predictors of metastases
No. (%)
|
||||||
---|---|---|---|---|---|---|
Neg
|
Single
|
Double
|
Triple
|
Total
|
P Value
|
|
(1–10 fold)
|
>10 fold
|
|||||
(
n = 37)
|
(
n = 101)
|
(
n = 172)
|
(
n = 122)
|
(
n = 432)
|
||
Basic Characteristics
|
||||||
Age
|
||||||
< 45
|
2 (5.4)
|
5 (5.0)
|
12 (7.0)
|
9 (7.4)
|
28
|
0.057
|
45-60
|
22 (59.5)
|
50 (49.5)
|
61 (35.5)
|
43 (35.2)
|
176
|
|
> 60
|
13 (35.1)
|
46 (45.5)
|
99 (57.6)
|
70 (57.4)
|
228
|
|
Sex
|
||||||
Male
|
27 (73.0)
|
71 (70.3)
|
114 (66.3)
|
84 (68.9)
|
296
|
0.827
|
Female
|
10 (27.0)
|
30 (29.7)
|
58 (33.7)
|
38 (31.1)
|
136
|
|
Histological classification
|
||||||
SCC
|
12 (32.4)
|
29 (28.7)
|
49 (28.5)
|
29 (23.8)
|
119
|
0.772
|
ADC
|
19 (51.4)
|
53 (52.5)
|
90 (52.3)
|
63 (51.6)
|
225
|
|
SCLC
|
3 (8.1)
|
12 (11.9)
|
24 (14)
|
24 (19.7)
|
63
|
|
Others
|
3 (8.1)
|
7 (6.9)
|
9 (5.2)
|
6 (4.9)
|
25
|
|
Stages
|
||||||
I
|
5 (13.5)
|
8 (7.9)
|
5 (2.9)
|
0 (0)
|
18
|
<0.05*
|
II
|
2 (5.4)
|
6 (5.9)
|
5 (2.9)
|
4 (3.3)
|
17
|
|
III
|
14 (37.8)
|
34 (33.7)
|
43 (25)
|
37 (30.3)
|
128
|
|
IV
|
14 (37.8)
|
47 (46.5)
|
109 (63.4)
|
73 (59.8)
|
243
|
|
#Un.
|
2 (5.4)
|
6 (5.9)
|
10 (5.8)
|
8 (6.6)
|
26
|
|
Smoke status
|
||||||
No
|
16 (43.2)
|
54 (53.5)
|
73 (42.4)
|
48 (39.3)
|
191
|
0.178
|
Yes
|
21 (56.8)
|
47 (46.5)
|
99 (57.6)
|
74 (60.7)
|
241
|
|
Metastasis
|
||||||
Brain
|
||||||
No
|
34 (91.9)
|
91 (90.1)
|
143 (83.1)
|
103 (84.4)
|
371
|
0.277
|
Yes
|
3 (8.1)
|
10 (9.9)
|
29 (16.9)
|
19 (15.6)
|
61
|
|
Bone
|
||||||
No
|
33 (89.2)
|
87 (86.1)
|
127 (73.8)
|
88 (72.1)
|
335
|
<0.05*
|
Yes
|
4 (10.8)
|
14 (13.9)
|
45 (26.2)
|
34 (27.9)
|
97
|
|
Liver
|
||||||
No
|
36 (97.3)
|
94 (93.1)
|
155 (90.1)
|
106 (86.9)
|
391
|
0.199
|
Yes
|
1 (2.7)
|
7 (6.9)
|
17 (9.9)
|
16 (13.1)
|
41
|
|
Adrenal gland
|
||||||
No
|
36 (97.3)
|
98 (97)
|
154 (89.5)
|
117 (95.9)
|
405
|
0.086
|
Yes
|
1 (1.7)
|
3 (3.0)
|
18 (10.5)
|
5 (4.1)
|
27
|
|
Lymph node
|
||||||
No
|
25 (67.6)
|
45 (44.6)
|
69 (40.1)
|
32 (26.2)
|
171
|
<0.001**
|
Yes
|
12 (32.4)
|
56 (55.4)
|
103 (59.9)
|
90 (73.8)
|
261
|
|
Intrapulmonary
|
||||||
No
|
33 (89.2)
|
89 (88.1)
|
149 (86.6)
|
108 (88.5)
|
379
|
0.950
|
Yes
|
4 (10.8)
|
12 (11.9)
|
23 (13.4)
|
14 (11.5)
|
53
|
|
Pleural
|
||||||
No
|
33 (89.2)
|
89 (88.1)
|
142 (82.6)
|
104 (85.2)
|
368
|
0.552
|
Yes
|
4 (10.8)
|
12 (11.9)
|
30 (17.4)
|
18 (14.8)
|
64
|
|
Mediastinal
|
||||||
No
|
37 (100)
|
98 (97)
|
169 (98.3)
|
114 (93.4)
|
418
|
0.080
|
Yes
|
0 (0.0)
|
3 (3.0)
|
3 (1.7)
|
8 (6.6)
|
14
|
|
Peritoneum
|
||||||
No
|
37 (100)
|
98 (93.7)
|
162 (94.2)
|
112 (91.8)
|
409
|
0.153
|
Yes
|
0 (0.0)
|
3 (6.3)
|
10 (5.8)
|
10 (8.2)
|
23
|
|
Validation group
|
||||||
No. (%)
|
||||||
Neg
|
Single
|
Double
|
Triple
|
Total
|
P Value
|
|
(
n = 27)
|
(
n = 118)
|
(
n = 161)
|
(
n = 130)
|
(
n = 436)
|
||
Basic Characteristics
|
||||||
Age
|
||||||
2 (7.4)
|
8 (6.8)
|
10 (6.2)
|
11 (8.5)
|
31
|
0.733
|
|
10 (37.0)
|
46 (39.0)
|
48 (29.8)
|
45 (34.6)
|
149
|
||
15 (55.6)
|
64 (54.2)
|
103 (64.0)
|
74 (56.9)
|
256
|
||
Sex
|
||||||
18 (66.7)
|
75 (63.6)
|
116 (72.0)
|
98 (75.4)
|
307
|
0.204
|
|
9 (33.3)
|
43 (36.4)
|
45 (28.0)
|
32 (24.6)
|
129
|
||
Histological classification
|
||||||
7 (25.9)
|
31 (26.3)
|
37 (23)
|
21 (16.2)
|
96
|
0.386
|
|
15 (55.6)
|
57 (48.3)
|
84 (52.2)
|
64 (49.2)
|
220
|
||
1 (3.7)
|
5 (4.2)
|
11 (6.8)
|
7 (5.4)
|
24
|
||
5 (18.5)
|
12 (10.2)
|
7 (4.3)
|
24 (18.5)
|
47
|
||
Stages
|
||||||
5 (18.5)
|
9 (7.6)
|
5 (3.1)
|
3 (2.3)
|
22
|
<0.05*
|
|
5 (18.5)
|
16 (13.6)
|
10 (6.2)
|
7 (5.4)
|
38
|
||
6 (22.2)
|
26 (22.0)
|
36 (22.4)
|
21 (16.2)
|
89
|
||
11 (40.7)
|
58 (49.2)
|
103 (64.0)
|
90 (69.2)
|
262
|
||
0 (0.0)
|
9 (7.6)
|
7 (4.3)
|
9 (19.2)
|
25
|
||
Smoke status
|
||||||
15 (55.6)
|
62 (52.5)
|
65 (40.4)
|
49 (37.7)
|
191
|
<0.05*
|
|
12 (44.4)
|
56 (47.5)
|
96 (59.6)
|
81 (62.3)
|
245
|
||
Metastasis
|
||||||
Brain
|
||||||
27 (100.0)
|
107 (90.7)
|
134 (83.2)
|
110 (84.6)
|
378
|
<0.05*
|
|
0 (0.0)
|
11 (9.3)
|
27 (16.8)
|
20 (15.4)
|
58
|
||
Bone
|
||||||
27 (100.0)
|
103 (87.3)
|
123 (76.4)
|
87 (66.9)
|
340
|
<0.001**
|
|
0 (0.0)
|
15 (12.7)
|
38 (23.6)
|
43 (33.1)
|
96
|
||
Liver
|
||||||
No
|
26 (96.3)
|
111 (94.1)
|
140 (87.0)
|
106 (81.5)
|
383
|
<0.05*
|
Yes
|
1 (3.7)
|
7 (5.9)
|
21 (13.0)
|
24 (18.5)
|
53
|
|
Adrenal gland
|
||||||
27 (100.0)
|
111 (94.1)
|
149 (92.5)
|
122 (93.8)
|
409
|
0.525
|
|
0 (0.0)
|
7 (5.9)
|
12 (7.5)
|
8 (6.2)
|
27
|
||
Lymph node
|
||||||
19 (70.4)
|
58 (49.2)
|
50 (31.1)
|
40 (30.8)
|
167
|
<0.001***
|
|
8 (29.6)
|
60 (50.8)
|
111 (68.9)
|
90 (69.2)
|
269
|
||
Intrapulmonary
|
||||||
26 (96.3)
|
105 (89.0)
|
130 (80.7)
|
114 (87.7)
|
375
|
0.064
|
|
1 (3.7)
|
13 (11.0)
|
31 (19.3)
|
16 (12.3)
|
61
|
||
Pleural
|
||||||
25 (92.6)
|
107 (90.7)
|
129 (80.1)
|
104 (80.0)
|
365
|
<0.05*
|
|
2 (7.4)
|
11 (9.3)
|
32 (20.8)
|
26 (20.0)
|
71
|
||
Mediastinal
|
||||||
27 (100.0)
|
116 (98.3)
|
152 (94.4)
|
123 (94.6)
|
418
|
0.229
|
|
0 (0.0)
|
2 (1.7)
|
9 (5.6)
|
7 (5.4)
|
18
|
||
Peritoneum
|
||||||
27 (100.0)
|
110 (93.2)
|
144 (89.4)
|
118 (90.8)
|
399
|
0.269
|
|
0 (0.0)
|
8 (6.8)
|
17 (10.4)
|
12 (9.2)
|
37
|
CYFRA21-1 levels correlated with survival in ADC, SCC and SCLC
Multivariate Cox regression analysis to identify poor prognostic factors
Multivariate HR (95% CI)
|
P value
|
|
---|---|---|
Age
|
||
< 45
|
1[Reference]
|
<0.001*
|
45–65
|
0.714 (0.513–0.994)
|
|
> 65
|
1.089 (0.793–1.495)
|
|
Sex
|
||
Male
|
1[Reference]
|
0.529
|
Female
|
0.942 (0.782–1.135)
|
|
Histological classification
|
||
Squamous
|
1[Reference]
|
<0.05*
|
Adenocarcinoma
|
1.113 (0.894–1.384)
|
|
SCLC
|
0.970 (0.729–1.290)
|
|
Others
|
1.654 (1.160–2.358)
|
|
Stages
|
||
I
|
1[Reference]
|
<0.05*
|
II
|
1.096 (0.624–1.925)
|
|
III
|
1.218 (0.753–1.969)
|
|
IV
|
1.976 (1.120–3.488)
|
|
Smoke statues
|
||
No
|
1[Reference]
|
0.095
|
Yes
|
0.823 (0.655–1.035)
|
|
CEA levels
|
||
Neg
|
1[Reference]
|
0.233
|
Moderate
|
1.171 (0.954–1.438)
|
|
High
|
1.217 (0.945–1.567)
|
|
CYFRA levels
|
||
Neg
|
1[Reference]
|
<0.001*
|
Moderate
|
1.226 (0.977–1.537)
|
|
High
|
1.647 (1.273–2.130)
|
|
NSE levels
|
||
Neg
|
1[Reference]
|
<0.05*
|
Moderate
|
1.010 (0.808–1.263)
|
|
High
|
1.330 (1.032–1.715)
|
|
Metastasis
|
||
No
|
1[Reference]
|
<0.05*
|
Yes
|
1.291 (1.025–1.625
|
|
Positive numbers
|
||
Neg
|
1[Reference]
|
0.649
|
Single
|
1.075 (0.806–1.434)
|
|
Double
|
1.102 (0.898–1.353)
|
|
Triple
|
1.086 (0.773–1.524)
|
Adenocarcinoma
|
Squamous
|
SCLC
|
||||
---|---|---|---|---|---|---|
(
n = 445)
|
(
n = 215)
|
(
n = 159)
|
||||
HR (95% CI)
|
P value
|
HR (95% CI)
|
P value
|
HR (95% CI)
|
P value
|
|
Age
|
||||||
< 45
|
1[Reference]
|
<0.05*
|
1[Reference]
|
<0.05*
|
1[Reference]
|
0.104
|
45–65
|
0.733 (0.489–1.099)
|
0.866 (0.259–2.895)
|
0.769 (0.315–1.876)
|
|||
> 65
|
1.084 (0.741–1.587)
|
1.712 (0.523–5.607)
|
1.237 (0.510–3.003)
|
|||
Sex
|
||||||
Male
|
1[Reference]
|
0.338
|
1[Reference]
|
0.326
|
1[Reference]
|
0.354
|
Female
|
0.986 (0.715–1.122)
|
1.312 (0.763–2.254)
|
0.758 (0.421–1.363)
|
|||
Stages
|
||||||
I + II
|
1[Reference]
|
0.415
|
1[Reference]
|
0.475
|
1[Reference]
|
0.902
|
III + IV
|
1.703 (1.035–2.802)
|
0.832 (0.495–1.399)
|
1.091 (0.465–2.556)
|
|||
Smoke status
|
||||||
No
|
1[Reference]
|
0.177
|
1[Reference]
|
0.878
|
1[Reference]
|
0.076
|
Yes
|
0.807 (0.592–1.102)
|
1.037 (0.651–1.651)
|
0.518 (0.251–1.071)
|
|||
CEA levels
|
||||||
Neg
|
1[Reference]
|
0.773
|
1[Reference]
|
0.295
|
1[Reference]
|
0.940
|
Moderate
|
1.085 (0.679–1.736)
|
1.244 (0.620–2.497)
|
0.850 (0.317–2.280)
|
|||
High
|
1.169 (0.713–1.916)
|
0.700 (0.260–1.885)
|
0.894 (0.271–2.942)
|
|||
CYFRA levels
|
||||||
Neg
|
1[Reference]
|
<0.05*
|
1[Reference]
|
0.195
|
1[Reference]
|
<0.05*
|
Moderate
|
1.161 (0.678–1.989)
|
1.057 (0.511–2.185)
|
1.365 (0.514–3.624)
|
|||
High
|
1.860 (1.036–3.338)
|
1.502 (0.673–3.353)
|
0.907 (0.285–2.880)
|
|||
NSE levels
|
||||||
Neg
|
1[Reference]
|
0.400
|
1[Reference]
|
0.329
|
1[Reference]
|
0.642
|
Moderate
|
1.025 (0.727–1.446)
|
1.025 (0.727–1.446)
|
0.952 (0.390–2.323)
|
|||
High
|
1.154 (0.777–1.714)
|
1.154 (0.777–1.714)
|
1.342 (0.590–3.052)
|
|||
Metastasis
|
||||||
No
|
1[Reference]
|
0.477
|
1[Reference]
|
<0.05*
|
1[Reference]
|
<0.05*
|
Yes
|
1.131 (0.806–1.585)
|
1.682 (1.052–2.688)
|
2.172 (1.180–3.998)
|
|||
Positive numbers
|
||||||
Neg
|
1[Reference]
|
0.852
|
1[Reference]
|
0.334
|
1[Reference]
|
0.814
|
Single
|
1.334 (0.672–2.649)
|
0.748 (0.300–1.863)
|
2.107 (0.460–9.644)
|
|||
Double
|
1.491 (0.557–3.992)
|
1.115 (0.327–3.803)
|
2.247 (0.386–13.077)
|
|||
Triple
|
1.652 (0.517–5.276)
|
0.901 (0.183–4.449)
|
2.508 (0.231–27.287)
|
Multivariate HR (95% CI)
|
P value
|
|
---|---|---|
A I + II
|
||
Age
|
||
< 45
|
1[Reference]
|
0.405
|
45–65
|
0.390 (0.043–3.577)
|
|
> 65
|
0.664 (0.075–5.874)
|
|
Sex
|
||
Male 1[Reference]
|
0.997
|
|
Female
|
0.998 (0.358–2.779)
|
|
Smokes
|
||
No
|
1[Reference]
|
0.828
|
Yes
|
1.091 (0.496–2.400)
|
|
Histological classification
|
||
SCC
|
1[Reference]
|
0.400
|
ADC
|
0.692 (0.294–1.631)
|
|
SCLC
|
1.000 (0.347–2.884)
|
|
Unknown
|
0.943 (0.242–3.670)
|
|
Metastasis
|
||
No
|
1[Reference]
|
0.992
|
Yes
|
0.997 (0.505–1.967)
|
|
CEA
|
||
Neg
|
1[Reference]
|
0.483
|
Moderate
|
1.213 (0.555–2.651)
|
|
High
|
1.442 (0.519–4.009)
|
|
NSE
|
||
Neg
|
1[Reference]
|
0.592
|
Moderate
|
1.064 (0.542–2.090)
|
|
High
|
0.718 (0.214–2.411)
|
|
CYFRA
|
||
Neg
|
1[Reference]
|
<0.05*
|
Moderate
|
1.696 (0.848–3.390)
|
|
High
|
3.666 (1.095–12.279)
|
|
B. Stage III
|
||
Age
|
||
< 45
|
1[Reference]
|
0.147
|
45–65
|
0.492 (0.189–1.283)
|
|
> 65
|
1.230 (0.491–3.083)
|
|
Sex
|
||
Male
|
1[Reference]
|
0.934
|
Female
|
0.976 (0.555–1.718)
|
|
Smokes
|
||
No
|
1[Reference]
|
0.758
|
Yes
|
1.075 (0.680–1.699)
|
|
Histological classification
|
||
SCC
|
1[Reference]
|
0.272
|
ADC
|
0.974 (0.624–1.521)
|
|
SCLC
|
0.796 (0.445–1.424)
|
|
Unknown
|
1.439 (0.752–2.756)
|
|
Metastasis
|
||
No
|
1[Reference]
|
0.094
|
Yes
|
1.444 (0.939–0.221)
|
|
CEA
|
||
Neg
|
1[Reference]
|
0.423
|
Moderate
|
1.047 (0.715–1.532)
|
|
High
|
1.260 (0.716–2.218)
|
|
NSE
|
||
Neg
|
1[Reference]
|
0.165
|
Moderate
|
0.738 (0.480–1.134)
|
|
High
|
1.333 (0.796–2.323)
|
|
CYFRA
|
||
Neg
|
1[Reference]
|
<0.05*
|
Moderate
|
1.279 (0.844–1.938)
|
|
High
|
1.919 (1.200–3.071)
|
|
C Stage IV
|
||
Age
|
||
< 45
|
1[Reference]
|
0.285
|
45–65
|
0.818 (0.566–1.182)
|
|
> 65
|
1.052 (0.739–1.499)
|
|
Sex
|
||
Male
|
1[Reference]
|
0.452
|
Female
|
1.125 (0.827–1.531)
|
|
Smokes
|
||
No
|
1[Reference]
|
0.130
|
Yes
|
1.261 (0.934–1.702)
|
|
Histological classification
|
||
SCC
|
1[Reference]
|
0.090
|
ADC
|
1.299 (0.960–1.756)
|
|
SCLC
|
1.182 (0.801–1.744)
|
|
Unknown
|
1.811 (1.082–3.030)
|
|
Metastasis
|
||
No
|
1[Reference]
|
<0.05*
|
Yes
|
1.494 (1.034–2.160)
|
|
CEA
|
||
Neg
|
1[Reference]
|
0.332
|
Moderate
|
1.132 (0.881–1.456)
|
|
High
|
1.074 (0.802–1.439)
|
|
NSE
|
||
Neg
|
1[Reference]
|
0.060
|
Moderate
|
1.042 (0.806–1.346)
|
|
High
|
1.319 (0.989–1.759)
|
|
CYFRA
|
||
Neg
|
1[Reference]
|
<0.05*
|
Moderate
|
1.107 (0.822–1.489)
|
|
High
|
1.473 (1.056–2.053)
|