It could be seen from Table 2 and Table 3 that gastric cancer was significantly related to the gender and age of patients (P < 0.001). Males accounted for 73.9% of the gastric cancer group,
Table 1
Distribution of Tumor Markers levels with Gastric cancer and Control
Tumor markers
|
Gastric Cancer (n = 268)
|
Control (n = 209)
|
|
Min
|
Max
|
Upper limit of 95% reference value
|
Min
|
Max
|
Upper limit of 95% reference value
|
AFP(ng/ml)
|
0.24
|
300.00
|
10.00
|
0.24
|
9.40
|
3.69
|
NSE(ng/ml)
|
1.26
|
57.47
|
6.83
|
1.32
|
8.00
|
4.33
|
FER(ng/ml)
|
2.21
|
519.46
|
412.3175
|
3.97
|
485.74
|
376.87
|
CEA(ng/ml)
|
0.23
|
60.00
|
50.38
|
0.20
|
10.88
|
3.18
|
CA125(U/ml)
|
1.43
|
500.00
|
231.31
|
1.70
|
147.25
|
20.46
|
CA153(U/ml)
|
1.08
|
176.79
|
23.06
|
1.46
|
75.00
|
24.46
|
CA199(U/ml)
|
2.00
|
455.13
|
384.08
|
0.56
|
46.00
|
24.23
|
CA242(U/ml)
|
1.00
|
200
|
143.67
|
1.00
|
24.61
|
7.61
|
AFP, alpha fetoprotein; NSE, neuron-specific enolase; FER, Ferritin; CEA, carcinoembryonic antigen; CA125, carbohydrate antigen 125; CA153, carbohydrate antigen 153; CA199, carbohydrate antigen 199; CA242, carbohydrate antigen 242 and the risk of the male suffering from gastric cancer was 3.329 times that of female; the age group over 54 years old in gastric cancer patients which accounted for 70.89%, and the risk of gastric cancer was 6.342 times that of the patient under 54 years.
Table 2. The relationship between gastric cancer and multiple tumor markers stratified by gender.
Tumor markers
|
Gender
|
Gastric cancer(n=268)
|
Control(n=209)
|
χ2
|
OR95%CI
|
P
|
/
|
Female
Male
|
70
|
113
|
|
|
|
/
|
198
|
96
|
38.787
|
3.329(2.265-4.893)
|
<0.001
|
AFP-
|
Female
|
60
|
105
|
|
|
|
Male
|
165
|
94
|
|
|
|
AFP+
|
Female
|
10
|
8
|
|
|
|
Male
|
33
|
2
|
15.043
|
3.803(1.862-7.767)
|
<0.001
|
NSE-
|
Female
|
62
|
110
|
|
|
|
Male
|
179
|
89
|
|
|
|
NSE+
|
Female
|
8
|
3
|
4.592
|
2.229(1.054-4.717)
|
0.038
|
Male
|
19
|
7
|
FER-
|
Female
|
67
|
113
|
|
|
|
Male
|
185
|
86
|
|
|
|
FER+
|
Female
|
3
|
0
|
4.924
|
/
|
0.054
|
Male
|
13
|
10
|
1.330
|
0.604(0.255-1.433)
|
0.249
|
CEA-
|
Female
|
55
|
109
|
|
|
|
Male
|
146
|
90
|
|
|
|
CEA+
|
Female
|
15
|
4
|
35.449
|
6.633(3.318-13.261)
|
<0.001
|
Male
|
52
|
6
|
CA125-
|
Female
|
54
|
104
|
|
|
|
Male
|
161
|
95
|
|
|
|
CA125+
|
Female
|
16
|
9
|
23.022
|
4.906(2.429-9.905)
|
<0.001
|
Male
|
37
|
1
|
CA153-
|
Female
|
66
|
109
|
|
|
|
Male
|
191
|
90
|
|
|
|
CA153+
|
Female
|
4
|
4
|
0.129
|
0.852(0.355-2.046)
|
0.719
|
Male
|
7
|
6
|
CA199-
|
Female
|
54
|
104
|
|
|
|
Male
|
150
|
95
|
|
|
|
CA199+
|
Female
|
16
|
9
|
8.128
|
3.424(1.420-8.257)
|
0.004
|
Male
|
48
|
1
|
25.057
|
30.400(4.127-223.928)
|
<0.001
|
CA242-
|
Female
|
54
|
104
|
|
|
|
Male
|
149
|
95
|
|
|
|
CA242+
|
Female
|
16
|
9
|
8.128
|
3.424(1.644-4.446)
|
0.004
|
Male
|
49
|
1
|
25.741
|
31.242(4.243-230.043)
|
<0.001
|
OR: odds ratio; CI: confidence interval;
Table 3. The relationship between gastric cancer and multiple tumor markers stratified by age.
Variable
|
Age
|
Gastric Cancer (n=268)
|
Control (n=209)
|
χ2
|
OR95%CI
|
P
|
/
|
≤54
|
78
|
151
|
|
|
|
/
|
>54
|
190
|
58
|
87.571
|
6.342(4.245-9.474)
|
<0.001
|
AFP-
|
≤54
|
69
|
144
|
|
|
|
|
>54
|
156
|
55
|
|
|
|
AFP+
|
≤54
|
9
|
7
|
15.074
|
3.803(1.862-7.767)
|
<0.001
|
|
>54
|
34
|
6
|
NSE-
|
≤54
|
73
|
141
|
|
|
|
|
>54
|
168
|
58
|
|
|
|
NSE+
|
≤54
|
5
|
10
|
4.592
|
2.580(1.050-6.336)
|
0.032
|
|
>54
|
22
|
0
|
FER-
|
≤54
|
76
|
141
|
|
|
|
|
>54
|
176
|
58
|
|
|
|
FER+
|
≤54
|
2
|
10
|
1.706
|
0.371(0.079-1.737)
|
0.229
|
|
>54
|
14
|
0
|
4.529
|
1.330(1.235-1.431)
|
0.045
|
CEA-
|
≤54
|
67
|
146
|
|
|
|
|
>54
|
134
|
53
|
|
|
|
CEA+
|
≤54
|
11
|
5
|
35.449
|
6.633(3.318-13.261)
|
<0.001
|
|
>54
|
56
|
5
|
CA125-
|
≤54
|
68
|
142
|
|
|
|
|
>54
|
147
|
57
|
|
|
|
CA125+
|
≤54
|
10
|
9
|
3.181
|
2.32(0.901-5.974)
|
0.082
|
|
>54
|
43
|
1
|
13.309
|
16.673(2.243-123.91)
|
<0.001
|
CA153-
|
≤54
|
75
|
142
|
|
|
|
|
>54
|
182
|
57
|
|
|
|
CA153+
|
≤54
|
3
|
9
|
0.129
|
0.852(0.355-2.046)
|
0.719
|
|
>54
|
8
|
1
|
CA199-
|
≤54
|
66
|
144
|
|
|
|
|
>54
|
138
|
55
|
|
|
|
CA199+
|
≤54
|
12
|
7
|
32.670
|
6.243(3.117-12.503)
|
<0.001
|
|
>54
|
52
|
3
|
CA242-
|
≤54
|
66
|
144
|
|
|
|
|
>54
|
137
|
55
|
|
|
|
CA242+
|
≤54
|
12
|
7
|
33.589
|
6.372(3.184-12.753)
|
<0.001
|
|
>54
|
53
|
3
|
OR: odds ratio; CI: confidence interval;
It showed in Figure 2 that the positive of AFP, CEA, CA125, CA199, and CA242 was significantly correlated with gastric cancer (P<0.001). To further explore the impact of gender, and age on tumor markers, we conducted a group study based on gender and age.
The relationship between gastric cancer and multiple tumor markers stratified by gender.
It showed in Table 2 that the positive of AFP(OR=3.803), CEA(OR=6.633), CA125(OR=4.906), CA199, and CA242 was significantly correlated with gastric cancer (P<0.001). After CA199 was stratified by gender. In the male, the OR was 30.400, 95% CI was 4.127-223.928, P<0.001, the risk of CA199-positive was 30.4 times than that of CA199-negative suffering from gastric cancer. In the female, CA199-positive was also a risk factor for gastric cancer. The OR was 3.424, 95% CI was 1.420-8.257, P=0.004, the risk of CA199-positive was 3.424 times than that of CA199-negative suffering from gastric cancer; After CA242 was stratified by gender, in male, the OR was 31.242, 95% CI was 4.243-230.043, P<0.001, the risk of CA242-positive was 31.242 times than that of CA242-negative suffering from gastric cancer. In the female, CA242-positive was also a risk factor for gastric cancer. The OR was 3.424 and 95% CI was 1.420-8.257, P=0.004, the risk of CA242-positive was 3.424 times than that of CA242-negative suffering from gastric cancer.
The relationship between gastric cancer and multiple tumor markers stratified by age.
It could be seen from Table 3 that the positive of AFP (OR=3.803), CEA (OR=6.633), CA125, CA199 (OR=6.234), CA242 (OR=6.372) was significantly related to gastric cancer (P<0.001), After CA125 was stratified by age, patients with older than 54 years, the OR was 16.673, 95% CI was 2.243-123.91, P<0.001, that was, the risk of CA125-positive was 16.673 times than that of CA125-negative suffering from gastric cancer; While less than or equal to 54 years old people, CA125 positive was not a risk factor for the disease. The OR was 2.32, the 95% CI was 0.901-5.974, and P=0.082.
The relationship between gastric cancer distant metastasis and tumor markers.
We further studied the relationship between gastric cancer distant metastasis and tumor markers. From Table 4 and Figure 3, we could see that as the staging of gastric cancer was delayed, the proportion of positive tumor markers increased, and AFP, CEA, CA125, CA199, CA242 in the M1 stage were statistically significant compared with the M0 stage and control group ((P<0.001), but AFP (P=0.045) and CA125 (P=0.752) were not statistically significant compared with the M0 stage and control group.
Table 4. Difference of tumor markers between M stage
Variable
|
AFP+
|
AFP-
|
CEA+
|
CEA-
|
CA125+
|
CA125-
|
CA199+
|
CA199-
|
CA242+
|
CA242-
|
Control
|
10
|
199
|
10
|
199
|
10
|
199
|
10
|
199
|
10
|
199
|
M0(201)
|
20
|
181
|
34
|
167
|
11
|
190
|
29
|
172
|
30
|
171
|
M1(67)
|
23
|
44
|
33
|
34
|
42
|
25
|
35
|
32
|
35
|
32
|
χ21
|
4.031
|
|
15.739
|
|
0.100
|
|
11.069
|
|
11.967
|
|
P1
|
0.045*
|
|
<0.001
|
|
0.752*
|
|
0.001
|
|
0.001
|
|
χ22
|
42.067
|
|
76.282
|
|
111.241
|
|
83.725
|
|
83.725
|
|
P2
|
<0.001
|
|
<0.001
|
|
<0.001
|
|
<0.001
|
|
<0.001
|
|
χ23
|
22.169
|
|
28.027
|
|
103.680
|
|
39.521
|
|
38.083
|
|
P3
|
<0.001
|
|
<0.001
|
|
<0.001
|
|
<0.001
|
|
<0.001
|
|
χ21, P1 M0 vs control, χ22, P2 M1 vs control, χ23, P3 M0 vs M1
* AFP (P=0.045) and CA125 (P=0.752) were not statistically significant compared with M0 stage and control group
Table 5. Sensitivity, specificity, and accuracy of single and multiple serum tumor markers
Tumor marker
|
Sensitivity (%)
|
Specificity (%)
|
Accuracy (%)
|
|
M0+M1
|
M0
|
M1
|
|
|
AFP
|
16.04(43/268)
|
9.95(20/201)
|
34.33(23/67)
|
95.22(199/209)
|
50.73(242/477)
|
CEA
|
25.00(67/268)
|
16.92(34/201)
|
49.25(33/67)
|
95.22(199/209)
|
55.77(266/477)
|
CA125
|
19.78(53/268)
|
5.47(11/201)
|
62.69(42/67)
|
95.22(199/209)
|
52.83(252/477)
|
CA199
|
23.88(64/268)
|
14.43(29/201)
|
52.24(35/67)
|
95.22(199/209)
|
55.14(263/477)
|
CA242
|
24.25(65/268)
|
14.93(30/201)
|
52.24(35/67)
|
95.22(199/209)
|
55.35(264/477)
|
Combination
|
41.79(112/268)
|
29.35(59/201)
|
79.10(53/67)
|
82.78(173/209)
|
59.75(285/477)
|
Sensitivity, specificity, and accuracy of single and multiple serum tumor markers
The results in Table 5 showed that the sensitivity of AFP, CEA, CA125, CA199, and CA242 to detect gastric cancer was 16.04%, 25.00%, 19.78%, 23.88%, 24.25%, and the sensitivity of combined detection of multiple tumor markers was 41.79%, which the specific was 82.78% and the accuracy was 59.75%. In the M0 stage, the sensitivity of AFP, CEA, CA125, CA199, and CA242 to detect gastric cancer was 9.95%, 16.92%, 5.47%, 14.43%, 14.93%, and the sensitivity of combined detection of multiple tumor markers was 29.35%. While in the M1 stage, the sensitivity of AFP, CEA, CA125, CA199, and CA242 to detect gastric cancer was 34.33%, 49.25%, 62.69%, 52.24%, 52.24%, and the sensitivity of combined detection of multiple tumor markers was 79.1%.