Prognostic value and predictive model of tumor markers in stage I to III gastric cancer patients

Table 1 Patient demographics and clinicopathologic features, n (%)

Variables	Patients (n = 1236)
Gender
Male	937 (75.8)
Female	299 (24.2)
Age
< 65	685 (55.4)
≥ 65	551 (44.6)
Drinking
Yes	269 (21.8)
No	967 (78.2)
Smoking
Yes	266 (21.5)
No	970 (78.5)
Operation methods
Open surgery	1103 (89.2)
Laparoscopic surgery	133 (10.8)
Hospitalization time
< 15 days	539 (43.6)
≥ 15 days	697 (56.4)
Clinical stage
I	288 (23.3)
II	272 (22.0)
III	676 (54.7)
T stage
T1	224 (18.1)
T2	127 (10.3)
T3	174 (14.1)
T4	711 (57.5)
N stage
N0	504 (40.8)
N1	203 (16.4)
N2	227 (18.4)
N3	302 (24.4)
Tumor location
Cardia	633 (51.2)
Gastric body	239 (19.3)
Antrum of stomach	364 (29.5)
Pathological type
Adenocarcinoma	1168 (94.5)
Mucinous adenocarcinoma	42 (3.4)
Squamous cell carcinoma	15 (1.2)
Signet ring cell carcinoma	11 (0.9)
Degree of differentiation
Well	19 (1.5)
High	42 (3.4)
Medium	300 (24.3)
Moderate to low	330 (26.7)
Poor	545 (44.1)
Borrmann type
I	155 (12.5)
II	287 (23.2)
III	737 (59.6)
IV	57 (4.7)
Size
< 5cm	690 (55.8)
≥ 5cm	546 (44.2)
Survival status
Alive	842 (68.1)
Dead	394 (31.9)

Table 2 The association of demographics and clinicopathologic characteristics with four serum tumor markers

Variables	AFP		P value	CEA		P value	CA125		P value	CA19-9		P value
	Positive (n = 1043)	Negative (n = 193)		Positive (n = 904)	Negative (n = 332)		Positive (n = 858)	Negative (n = 378)		Positive (n = 969)	Negative (n = 267)
Gender			0.200			0.072			0.072			0.809
Male	798	139		673	264		663	274		736	201
Female	245	54		231	68		195	104		233	66
Age			0.753			0.002			0.214			0.144
< 65	576	109		526	159		486	199		548	137
≥ 65	467	84		378	173		372	179		421	130
Clinical stage			0.034			0.000			0.000			0.000
I	257	31		263	25		242	46		278	10
II	227	45		208	64		196	76		240	32
III	559	117		433	243		420	256		451	225
T stage			0.855			0.000			0.000			0.000
T1	193	31		208	16		181	43		214	10
T2	108	19		104	23		110	17		121	6
T3	146	28		116	58		109	65		128	46
T4	596	115		476	235		458	253		506	205
N stage			0.005			0.000			0.000			0.000
N0	446	58		430	74		392	112		462	42
N1	171	32		150	53		145	58		166	37
N2	185	42		151	76		149	78		152	75
N3	241	61		173	129		172	130		189	113
Tumor location			0.082			0.000			0.221			0.041
Cardia	537	96		433	200		444	189		485	148
Gastric body	191	48		182	57		155	84		182	57
Antrum of stomach	315	49		289	75		259	105		302	62
Pathological type			1.000			0.324			0.417			0.045
Adenocarcinoma	985	183		858	310		814	354		919	249
Other	58	10		46	22		44	24		50	18
Degree of differentiation			0.606			0.049			0.014			0.002
Well, high, medium	308	53		278	83		269	92		303	58
Moderate to low, poor	735	140		626	249		589	286		666	209
Borrmann type			0.220			0.000			0.029			0.000
I and II	381	61		353	89		324	118		391	51
III and IV	662	132		551	243		534	260		578	216
Size			0.305			0.000			0.000			0.000
< 5	589	101		555	135		528	162		590	100
≥ 5	454	92		349	197		330	216		379	167
Survival status			0.000			0.000			0.000			0.000
Alive	736	106		686	156		646	196		728	114
Dead	307	87		218	176		212	182		241	153

AFP: Alpha foetoprotein; CEA: Carcinoembryonic antigen.

Table 3 Univariate and multivariate cox regression analysis for overall survival

Variables	OS
	HR (95%CI)	P value
Univariate analysis
Gender (male vs female)	0.922 (0.729-1.165)	0.496
Age (< 65 vs ≥ 65)	1.315 (1.080-1.604)	0.007
Clinical stage
I	1 (Reference)
II	2.876 (1.735-4.768)	0.000
III	8.712 (5.601-13.552)	0.000
T stage
T1	1 (Reference)
T2	1.693 (0.889-3.227)	0.019
T3	4.438 (2.634-7.478)	0.000
T4	6.330 (3.981-10.065)	0.000
N stage
N0	1 (Reference)
N1	2.330 (1.667-3.257)	0.000
N2	3.239 (2.383-4.401)	0.000
N3	5.201 (3.957-6.836)	0.000
Location
Cardia	1 (Reference)
Gastric body	1.306 (1.025-1.664)	0.031
Antrum of stomach	1.698 (1.276-2.261)	0.000
Pathological type (adenocarcinoma vs other)	1.209 (0.807-1.813)	0.358
Differentiation (well, high and medium vs moderate to low and poor)	1.776 (1.392-2.265)	0.000
Borrmann type (III vs other)	0.579 (0.462-0.724)	0.000
Size (< 5 vs ≥ 5)	0.403 (0.329-0.494)	0.000
AFP (positive vs negative)	1.929 (1.520-2.448)	0.000
CEA (positive vs negative)	3.155 (2.584-3.851)	0.000
CA125 (positive vs negative)	2.521 (2.067-3.074)	0.000
CA19-9 (positive vs negative)	3.489 (2.847-4.276)	0.000
Multivariate analysis
Age (< 65 vs ≥ 65)	1.225 (0.999-1.501)	0.052
Clinical stage
I	1 (Reference)
II	2.102 (1.248-3.540)	0.005
III	4.860 (2.988-7.907)	0.000
Location
Cardia	1 (Reference)
Gastric body	1.531 (1.187-1.976)	0.051
Antrum of stomach	1.092 (0.847-1.406)	0.498
Differentiation (well, high and medium vs moderate to low and poor)	1.212 (0.940-1.564)	0.139
Borrmann type (III vs other)	0.873 (0.688-1.108)	0.265
Size (< 5 vs ≥ 5)	1.269 (1.020-1.578)	0.032
AFP (positive vs negative)	1.728 (1.359-2.198)	0.000
CEA (positive vs negative)	2.037 (1.646-2.522)	0.000
CA125 (positive vs negative)	1.739 (1.416-2.135)	0.000
CA19-9 (positive vs negative)	1.910 (1.535-2.377)	0.000

OS: Overall survival; HR: Hazard ratio.

Table 4 Multivariate cox regression analysis and assigned scores about four tumor markers

Variables	OS
	HR (95%CI)	P value	β	Reference value	Score
AFP (positive vs negative)	1.722 (1.355-2.190)	0.000	0.543	0.543	1
CEA (positive vs negative)	2.311 (1.877-2.847)	0.000	0.838	0.543	2
CA125 (positive vs negative)	1.957 (1.595-2.401)	0.000	0.671	0.543	1
CA19-9 (positive vs negative)	2.504 (2.021-3.103)	0.000	0.920	0.543	2

AFP: Alpha foetoprotein; CEA: Carcinoembryonic antigen; OS: Overall survival; HR: Hazard ratio.

Table 5 The association of demographics and clinicopathologic characteristics with different scores

Variables	0 (n = 537)	1 (n = 219)	2 (n = 181)	3 (n = 139)	4 (n = 59)	5 (n = 71)	6 (n = 30)	P value
Gender								0.506
Male	413	158	136	104	50	55	21
Female	124	61	45	35	9	16	9
Age								0.179
< 65	316	124	98	68	31	36	12
≥ 65	221	95	83	71	28	35	18
Clinical stage								0.000
I	197	51	27	10	3	0	0
II	120	66	36	33	10	6	1
III	220	102	118	96	46	65	29
T stage								0.000
T1	147	48	15	10	3	0	1
T2	75	22	20	9	0	1	0
T3	56	37	27	25	13	13	3
T4	259	112	119	95	43	57	26
N stage								0.000
N0	292	96	64	36	11	4	1
N1	94	40	18	27	8	15	1
N2	73	37	44	32	14	17	10
N3	78	46	55	44	26	35	18
Tumor location								0.010
Cardia	268	95	97	77	37	41	18
Gastric body	93	58	28	26	11	14	9
Antrum of stomach	176	66	56	36	11	16	3
Pathological type								0.236
Adenocarcinoma	514	202	172	133	54	64	29
Other	23	17	9	6	5	7	1
Degree of differentiation								0.013
Well, high, medium	174	64	53	41	16	8	5
Moderate to low, poor	363	155	128	98	43	63	25
Borrmann type								0.000
I and II	241	80	42	48	10	15	6
III and IV	296	139	139	91	49	56	24
Size								0.000
< 5	364	121	91	66	17	22	9
≥ 5	173	98	90	73	42	49	21
Survival status
Alive	433	161	128	75	27	16	2
Dead	104	58	53	64	32	55	28

Table 6 Further comparison of variables with different score

Variables	P value
	Clinical stage	T stage	N stage	Location	Differentiation	Borrmann type	Size	Survival status
0 vs 1	0.001	0.027	0.036	0.016	0.437	0.035	0.001	0.032
0 vs 2	0.000	0.000	0.000	0.678	0.461	0.000	0.000	0.007
0 vs 3	0.000	0.000	0.000	0.296	0.541	0.034	0.000	0.000
0 vs 4	0.000	0.000	0.000	0.077	0.464	0.000	0.000	0.000
0 vs 5	0.000	0.000	0.000	0.218	0.000	0.000	0.000	0.000
0 vs 6	0.000	0.000	0.000	0.020	0.104	0.007	0.000	0.000
1 vs 2	0.001	0.001	0.005	0.021	0.990	0.005	0.365	0.575
1 vs 3	0.000	0.001	0.005	0.071	0.956	0.725	0.160	0.000
1 vs 4	0.000	0.001	0.000	0.030	0.872	0.005	0.000	0.000
1 vs 5	0.000	0.000	0.000	0.106	0.002	0.020	0.000	0.000
1 vs 6	0.000	0.002	0.000	0.061	0.193	0.100	0.011	0.000
2 vs 3	0.092	0.481	0.061	0.541	0.967	0.033	0.653	0.002
2 vs 4	0.095	0.032	0.072	0.187	0.869	0.366	0.004	0.001
2 vs 5	0.000	0.004	0.000	0.373	0.003	0.867	0.007	0.000
2 vs 6	0.002	0.101	0.001	0.026	0.188	0.817	0.048	0.000
3 vs 4	0.445	0.206	0.316	0.521	0.864	0.016	0.018	0.351
3 vs 5	0.001	0.036	0.003	0.867	0.003	0.056	0.027	0.000
3 vs 6	0.007	0.202	0.001	0.116	0.180	0.136	0.105	0.000
4 vs 5	0.045	0.180	0.114	0.824	0.024	0.657	0.849	0.008
4 vs 6	0.069	0.329	0.065	0.348	0.306	0.774	0.907	0.000
5 vs 6	0.671	0.282	0.133	0.252	0.520	0.899	0.922	0.086

Table 7 Means and 95%CI for overall survival in patients with different stages and different score of gastric cancer

Stage	Score	Mean overall survival time (months)
		Estimate	SE	95%CI
I	0 (n = 197)	56.200	0.516	55.188-57.212
	1 (n = 51)	56.893	0.777	55.371-58.416
	2 (n = 27)	52.090	2.283	47.615-56.564
	3 (n = 10)	44.700	3.985	36.889-52.511
	Overall (n = 285)	55.980	0.456	55.086-56.874
II	0 (n = 120)	54.133	0.946	52.279-55.987
	1 (n = 66)	49.802	1.778	46.316-53.288
	2 (n = 36)	53.627	1.320	51.039-56.214
	3 (n = 33)	44.903	3.293	38.449-51.357
	4 (n = 10)	38.400	6.442	25.773-51.027
	Overall (n = 265)	51.550	0.845	49.893-53.207
III	0 (n = 220)	46.927	1.052	44.864-48.989
	1 (n = 102)	44.814	1.727	41.429-48.199
	2 (n = 118)	43.357	1.661	40.102-46.613
	3 (n = 96)	35.471	2.129	31.298-39.645
	4 (n = 48)	31.096	3.157	24.909-37.283
	5 (n = 71)	20.462	2.271	16.010-24.913
	6 (n = 30)	10.966	2.240	6.576-15.355
	Overall (n = 676)	39.422	0.792	37.870-40.974