Application of preoperative artificial neural network based on blood biomarkers and clinicopathological parameters for predicting long-term survival of patients with gastric cancer

Table 1 General clinicopathological data, n (%)

Variable	All patients (n = 1608)	Training set (n = 1104)	Testing set (n = 504)
Age (yr)
< 57	593 (36.9)	413 (37.4)	180 (35.7)
57-74	838 (52.1)	565 (51.2)	273 (54.2)
> 74	177 (11.0)	126 (11.4)	51 (10.1)
Sex
Female	412 (25.6)	299 (27.1)	113 (22.4)
Male	1196 (74.4)	805 (72.9)	391 (77.6)
BMI
< 18.5	156 (9.7)	98 (8.9)	58 (11.5)
18.5-23.5	960 (59.7)	670 (60.7)	290 (57.5)
> 23.5	492 (30.6)	336 (30.4)	156 (31.0)
CEA
< 2.8	932 (58.0)	626 (56.7)	306 (60.7)
2.8-4.8	328 (20.4)	226 (20.5)	102 (20.2)
> 4.8	348 (21.6)	252 (22.8)	96 (19.0)
CA199
< 15.0	1043 (64.9)	696 (63.0)	347 (68.8)
15.0-39.2	348 (21.6)	255 (23.1)	93 (18.5)
> 39.2	217 (13.5)	153 (13.9)	64 (12.7)
AFP
< 2	496 (30.8)	344 (31.2)	152 (30.2)
2-5.29	916 (57.0)	631 (57.2)	285 (56.5)
> 5.3	196 (12.2)	129 (11.7)	67 (13.3)
NLR
< 1.91	632 (39.3)	422 (38.2)	210 (41.7)
1.91-3.87	753 (46.8)	525 (47.6)	228 (45.2)
> 3.87	223 (13.9)	157 (14.2)	66 (13.1)
PLR
< 89.5	258 (16.0)	177 (16.0)	81 (16.1)
89.5-162.3	777 (48.3)	540 (48.9)	237 (47.0)
>162.3	573 (35.6)	387 (35.1)	186 (36.9)
AGR
< 6.59	474 (29.5)	332 (30.1)	142 (28.2)
6.59-7.81	612 (38.1)	426 (38.6)	186 (36.9)
> 7.81	522 (32.5)	346 (31.3)	176 (34.9)
PNI
< 371	495 (30.8)	347 (31.4)	148 (29.4)
371-430	771 (47.9)	531 (48.1)	240 (47.6)
> 430	342 (21.3)	226 (20.5)	116 (23.0)
ASA
I	983 (61.1)	677 (61.3)	306 (60.7)
II	561 (34.9)	379 (34.3)	182 (36.1)
III-IV	64 (4.0)	48 (4.3)	16 (3.2)
Comorbidity
No	1133 (70.5)	779 (70.6)	354 (70.2)
Yes	475 (29.5)	325 (29.4)	150 (29.8)
Primary site
Lower	671 (41.7)	476 (43.1)	195 (38.7)
Middle	350 (21.8)	231 (20.9)	119 (23.6)
Upper	401 (24.9)	257 (23.3)	144 (28.6)
Overlapping	186 (11.6)	140 (12.7)	46 (9.1)
Tumor size (mm)
< 30	578 (35.9)	404 (36.6)	174 (34.5)
30-60	711 (44.2)	477 (43.2)	234 (46.4)
> 60	319 (19.8)	223 (20.2)	96 (19.0)
cT
T1	167 (10.4)	108 (9.8)	59 (11.7)
T2	185 (11.5)	135 (12.2)	50 (9.9)
T3	429 (26.7)	292 (26.4)	137 (27.2)
T4	827 (51.4)	569 (51.5)	258 (51.2)
cN
N0	662 (41.2)	457 (41.4)	205 (40.7)
N1	376 (23.4)	257 (23.3)	119 (23.6)
N2	362 (22.5)	245 (22.2)	117 (23.2)
N3	208 (12.9)	145 (13.1)	63 (12.5)
Follow-up duration (mo)	48 (3-91)	48 (3-91)	50 (3-89)

BMI: Body mass index; CEA: Carcinoembryonic antigen; CA199: Carbohydrate antigen 19-9; AFP: Alpha fetoprotein; NLR: Neutrophil-lymphocyte ratio; PLR: Platelet-lymphocyte ratio; AGR: Albumin-globulin ratio; PNI: Prognostic nutrition index; ASA: American society of anesthesiologists; cT: Clinical T stage; cN: Clinical N stage.

Table 2 Univariate logistics regression analysis of risk factors for the 3-year survival

Variable	Training set
	OR	95CI		P value
Age (yr)
< 57	REF
57-74	0.38	0.25	0.58	< 0.001
> 74	0.63	0.42	0.93	0.020
Sex
Male	REF
Female	0.96	0.72	1.29	0.782
BMI
< 18.5	REF
18.5-23.5	3.04	1.90	4.85	< 0.001
> 23.5	1.28 357	0.95	1.73	0.111
CEA
< 2.8	REF
2.8-4.8	0.33	0.24	0.45	< 0.001
> 4.8	0.46	0.31	0.67	< 0.001
CA199
< 15.0	REF
15.0-39.2	0.20	0.14	0.29	< 0.001
> 39.2	0.33	0.22	0.50	< 0.001
AFP
< 2	REF			< 0.001
2-5.29	0.78	0.51	1.18	0.240
> 5.3	0.50	0.33	0.74	0.001
NLR
< 1.91	REF
1.91-3.87	0.32	0.22	0.48	< 0.001
> 3.87	0.48	0.33	0.69	< 0.001
PLR
< 89.5	REF
89.5-162.3	0.26	0.16	0.42	< 0.001
> 162.3	0.59	0.45	0.78	< 0.001
AGR
< 6.59	REF
6.59-7.81	2.11	1.50	2.98	< 0.001
> 7.81	1.58	1.13	2.20	0.007
PNI
< 371	REF
371-430	3.98	2.62	6.06	< 0.001
> 430	1.94	1.29	2.92	0.002
ASA
I	REF
II	0.44	0.24	0.79	0.006
III-IV	0.53	0.29	0.97	0.041
Comorbidity
No	REF
Yes	0.99	0.74	1.31	0.933
Primary site
Lower	REF
Middle	0.30	0.20	0.45	< 0.001
Upper	0.54	0.35	0.83	0.001
Overlapping lesion of the stomach	0.47	0.31	0.73	< 0.001
Tumor size (mm)
< 30	REF
30-60	0.08	0.06	0.13	< 0.001
> 60	0.43	0.31	0.60	< 0.001
cT
T1	REF
T2	0.05	0.02	0.13	< 0.001
T3	0.18	0.11	0.32	< 0.001
T4	0.24	0.17	0.34	< 0.001
cN
N0	REF
N1	0.18	0.12	0.27	< 0.001
N2	0.28	0.18	0.43	< 0.001
N3	0.67	0.44	1.007	0.054

BMI: Body mass index; CEA: Carcinoembryonic antigen; CA199: Carbohydrate antigen 19-9; AFP: Alpha fetoprotein; NLR: Neutrophil-lymphocyte ratio; PLR: Platelet-lymphocyte ratio; AGR: Albumin-globulin ratio; PNI: Prognostic nutrition index; ASA: American society of anesthesiologists; cT: Clinical T stage; cN: Clinical N stage; OR: Odds ratio; CI: Confidence interval.

Table 3 Comparison of the area under the curve values and Harrell’s C index between the pathological TNM stage, clinical TNM stage, and preoperative artificial neural network

	Training set			Testing set			Bio-ANN	Cli-ANN
	Preope-ANN	cTNM	pTNM	Preope-ANN	cTNM	pTNM
Harrell’s C index	0.773 (0.753-0.795)	0.663 (0.640-0.687)	0.757 (0.735-0.779)	0.752 (0.719-0.785)	0.652 (0.615-0.688)	0.740 (0.707-0.775)	0.722 (0.698-0.746)	0.760 (0.738-0.782)
P value		< 0.001	0.120		< 0.001	0.539	aP < 0.001; bP = 0.000; cP = 0.018	dP < 0.001 eP < 0.000; fP = 0.827
AIC	4977.83	5176.70	4999.80	1952.94	2020.37	1951.84	5115.9	5011.9
Relative likelihood		< 0.001	< 0.001		<0.001	1.733	aP < 0.001; bP > 1 cP < 0.001	dP = 0.001 E > 1 fP = 0.06

^aP, Bio-artificial neural network (ANN) vs preoperative ANN (preope-ANN);

^bP, Bio-ANN vs clinical TNM (cTNM);

^cP, Bio-ANN vs pathological TNM (pTNM).

^dP, cli-ANN vs preope-ANN;

^eP, cli-ANN vs cTNM;

^fP, cli-ANN vs pTNM. pTNM: Pathological TNM; cTNM: Clinical TNM; preope-ANN: Preoperative artificial neural network; AIC: Akaike information criterion.