Development and validation of a prognostic immunoinflammatory index for patients with gastric cancer

Table 1 Clinicopathological characteristics, n (%)

Variable	All patients	Training set	Validation set
Age (years), mean (± SD)	59.05 (10.45)	58.45 (10.38)	60.48 (10.54)
Sex,
Male	203 (69.8)	144 (70.6)	59 (67.8)
Female	88 (30.2)	60 (29.4)	28 (32.2)
Body mass index (kg/m2), mean (SD)	22.86 (3.22)	22.95 (3.04)	22.65 (3.63)
Radical resection
Yes	274 (94.2)	195 (95.6)	79 (90.8)
No	17 (5.8)	9 (4.4)	8 (9.2)
Primary tumor site
Upper 1/3	11 (3.7)	8 (3.9)	3 (3.4)
Middle 1/3	38 (13.1)	28 (13.7)	10 (11.5)
Low 1/3	208 (71.5)	142 (69.7)	66 (75.9)
Whole	34 (11.7)	26 (12.7)	8 (9.2)
Borrmann type
Ⅰ	32 (11.0)	22 (10.8)	10 (11.5)
Ⅱ	87 (29.9)	63 (30.9)	24 (27.6)
Ⅲ	153 (52.6)	109 (53.4)	44 (50.6)
Ⅳ	19 (6.5)	10 (4.9)	9 (10.3)
Lymph node positivity
Yes	138 (47.4)	99 (48.5)	39 (44.8)
No	153 (52.6)	105 (51.5)	48 (55.2)
Tumor size
< 20 mm	29 (10.0)	18 (8.8)	11 (12.6)
20–50 mm	124 (42.6)	89 (43.6)	35 (40.2)
> 50 mm	138 (47.4)	97 (47.6)	41 (47.1)
Differentiation
Poor	101 (34.7)	72 (35.3)	29 (33.3)
Moderate	149 (51.2)	106 (52.0)	43 (49.4)
Well	26 (8.9)	19 (9.3)	7 (8.0)
Unknown	15 (5.2)	7 (3.4)	8 (9.3)
Lauren type
Intestinal	143 (49.1)	105 (51.5)	38 (43.7)
Diffuse	51 (17.5)	35 (17.2)	16 (18.4)
Mixed	84 (28.9)	58 (28.4)	26 (29.9)
Unknown	13 (4.5)	6 (2.9)	7 (8.0)
TNM stage
Ⅰ	117 (40.2)	81 (39.7)	36 (41.4)
Ⅱ	71 (24.4)	53 (26.0)	18 (20.7)
Ⅲ	89 (30.6)	62 (30.4)	27 (31.0)
Ⅳ	14 (4.8)	8 (3.9)	6 (6.9)
Carcinoembryonic antigen
< 1.97 ng/mL	144 (49.5)	107 (52.5)	37 (42.5)
≥ 1.97 ng/mL	147 (50.9)	97 (47.5)	50 (57.5)
CA199
< 10.19 U/L	145 (49.8)	103 (50.5)	42 (48.3)
≥ 10.19 U/L	146 (50.2)	101 (49.5)	45 (51.7)
CA724
< 2.17 U/L	145 (49.8)	106 (52.0)	39 (44.8)
≥ 2.17 U/L	146 (50.2)	98 (48.0)	48 (55.2)
CA125II
< 10.21 U/L	145 (49.8)	102 (50.0)	43 (49.4)
≥ 10.21 U/L	146 (50.2)	102 (50.0)	44 (50.6)
NLR, mean (SD)	2.63 (2.98)	2.62 (3.03)	2.66 (2.87)
PLR, mean (SD)	148.10 (7.47)	149.64 (78.22)	144.50 (68.87)
SII, mean (SD)	668.08 (768.43)	683.94 (796.04)	630.89 (702.44)
SIRI, mean (SD)	70.69 (29.36)	70.05 (24.26)	72.18 (38.93)
CD3(+) (%), mean (SD)	70.91 (38.40)	69.00 (9.31)	75.41 (68.84)
CD3(+)CD4(+) (%), mean (SD)	40.82 (8.67)	40.79 (8.22)	40.88 (9.69)
CD3(+)CD8(+) (%), mean (SD)	23.42 (8.07)	23.49 (8.02)	23.24 (8.25)
CD4(+)/CD8(+), mean (SD)	2.04 (1.08)	1.99 (0.92)	2.17 (1.37)
CD3(+)CD4(+)CD8(+) (%), mean (SD)	0.54 (1.23)	0.61 (1.44)	0.36 (0.37)
CD19(+) (%), mean (SD)	11.32 (4.71)	11.68 (4.76)	10.48 (4.51)
CD3(-)CD16(+)CD56(+) (%), mean (SD)	16.72 (9.55)	16.25 (8.34)	17.83 (11.02)
CD3(+)CD16(+)CD56(+) (%), mean (SD)	3.13 (4.34)	3.26 (4.89)	2.83 (2.63)

CA125II: Carbohydrate antigen 125II; CA199: Carbohydrate antigen 199; CA724: Carbohydrate antigen 724; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; SII: Systemic immune inflammatory index; SIRI: Systemic inflammation response index.

Table 2 Association between prognostic immunoinflammatory index score and clinical characteristics, n (%)

Variable	PII score		P value
	Group 1, n = 130	Group 2, n = 74
Age (years), mean (SD)	58.03 (10.52)	59.18 (10.17)	0.398
Sex			0.301
Male	95 (73.1)	49 (66.2)
Female	35 (26.9)	25 (33.8)
Body mass index (kg/m2), mean (SD)	23.38 (3.13)	22.19 (2.73)	0.004
Radical resection			0.075
Yes	127 (97.7)	68 (91.9)
No	3 (2.3)	6 (8.1)
Primary tumor site			0.016
Upper 1/3	4 (3.1)	4 (5.4)
Middle 1/3	17 (13.1)	11 (14.9)
Low 1/3	99 (76.1)	43 (58.1)
Whole	10 (7.7)	16 (21.6)
Borrmann type			0.275
Ⅰ	16 (12.3)	6 (8.1)
Ⅱ	43 (33.1)	20 (27.0)
Ⅲ	67 (51.5)	42 (56.8)
Ⅳ	4 (3.1)	6 (8.1)
Lymph node positivity
Yes	67 (47.7)	37 (50.0)
No	68 (52.3)	37 (50.0)
Tumor size			0.031
< 20 mm	14 (10.8)	4 (5.4)
20–50 mm	63 (48.5)	26 (35.1)
> 50 mm	53 (40.7)	44 (59.5)
Differentiation			0.100
Poor	43 (33.2)	29 (39.2)
Moderate	70 (53.8)	36 (48.6)
Well	15 (11.5)	4 (5.4)
Unknown	2 (1.5)	5 (6.8)
Lauren type			0.125
Intestinal	67 (51.5)	38 (51.4)
Diffuse	23 (17.7)	12 (16.2)
Mixed	39 (30.0)	19 (25.6)
Unknown	1 (0.8)	5 (6.8)
TNM stage			0.155
Ⅰ	52 (40.0)	29 (39.2)
Ⅱ	34 (26.2)	19 (25.7)
Ⅲ	42 (32.3)	20 (27.0)
Ⅳ	2 (1.5)	6 (8.1)
Carcinoembryonic antigen			0.729
< 1.97 ng/mL	67 (51.5)	40 (54.1)
≥1.97 ng/mL	63 (48.5)	34 (45.9)
CA199			0.032
< 10.19 U/L	73 (56.2)	30 (40.5)
≥ 10.19 U/L	57 (43.8)	44 (59.5)
CA724			0.056
< 2.17 U/L	61 (46.9)	45 (60.8)
≥ 2.17 U/L	69 (53.1)	29 (39.2)
CA125II			0.244
< 10.21 U/L	61 (46.9)	41 (55.4)
≥ 10.21 U/L	69 (53.1)	33 (44.6)
NLR, mean (SD)	1.69 (0.67)	4.24 (4.54)	< 0.001
PLR, mean (SD)	107.02 (31.74)	224.36 (79.72)	< 0.001
SII, mean (SD)	392.19 (180.21)	1196.46 (1134.42)	< 0.001
SIRI, mean (SD)	0.88 (0.48)	2.37 (3.27)	< 0.001
CD3(+) (%), mean (SD)	67.21 (9.87)	72.14 (7.30)	< 0.001
CD3(+)CD4(+) (%), mean (SD)	40.46 (8.14)	41.34 (8.38)	0.445
CD3(+)CD8(+) (%), mean (SD)	22.36 (7.60)	25.47 (8.40)	0.005
CD4(+)/CD8(+), mean (SD)	2.07 (0.94)	1.84 (0.87)	0.069
CD3(+)CD4(+)CD8(+) (%), mean (SD)	0.53 (0.73)	0.76 (2.20)	0.657
CD19(+) (%), mean (SD)	12.58 (4.89)	10.10 (4.09)	< 0.001
CD3(-)CD16(+)CD56(+) (%), mean (SD)	16.99 (9.71)	14.94 (6.92)	0.282
CD3(+)CD16(+)CD56(+) (%), mean (SD)	3.17 (5.48)	3.41 (3.67)	0.202

CA125II: Carbohydrate antigen 125II; CA199: Carbohydrate antigen 199; CA724: Carbohydrate antigen 724; NLR: Neutrophil-to-lymphocyte ratio; PII: Prognostic immunoinflammatory index; PLR: Platelet-to-lymphocyte ratio; SII: Systemic immune inflammatory index; SIRI: Systemic inflammation response index; TNM: Tumor-node-metastasis.

Table 3 COX regression analysis of overall survival and progression-free survival

Parameter	OS				PFS
	Univariate analysis		Multivariate analysis		Univariate analysis		Multivariate analysis
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Age (years)	2.035 (1.325-3.061)	0.001	1.541 (0.982-2.417)	0.051	1.978 (1.302-3.007)	0.001	1.488 (0.948-2.335)	0.084
Sex
Male	1 (Ref.)				1 (Ref.)
Female	0.912 (0.597-1.392)	0.669			0.918 (0.601-1.401)	0.692
Body mass index (kg/m2)	0.527 (0.342-0.811)	0.004	0.853 (0.536-1.357)	0.502	0.527 (0.342-0.812)	0.004	0.838 (0.526-1.334)	0.456
CD3(+) (%)	2.051 (1.387-3.033)	< 0.001			1.995 (1.350-2.949)	0.001
CD3(+)CD4(+) (%)	1.526 (0.961-2.424)	0.073			1.528 (0.963-2.426)	0.072
CD3(+)CD8(+) (%)	1.516 (1.034-2.221)	0.029			1.513 (1.003-2.217)	0.030
CD4(+)/CD8(+)	0523 (0.341-0.802)	0.002			0.517 (0.337-0.792)	0.002
CD3(+)CD4(+)CD8(+) (%)	1.516 (0.940-2.445)	0.088			1.504 (0.933-2.425)	0.094
CD19(+) (%)	0.351 (0.171-0.721)	0.003			0.358 (0.174-0.735)	0.004
CD3(-)CD16(+)CD56(+) (%)	0.703 (0.480-1.030)	0.070			0.712 (0.486-1.043)	0.082
CD3(+)CD16(+)CD56(+) (%)	1.880 (1.207-2.931)	0.005			1.865 (1.197-2.905)	0.005
PLR
< 2.81	1 (Ref.)				1 (Ref.)
≥ 2.81	1.913 (1.241-2.949)	0.003			1.898 (1.231-2.926)	0.003
NLR
< 115.22	1 (Ref.)				1 (Ref.)
≥ 155.22	2.390 (1.588)	< 0.001			2.338 (1.554-3.518)	< 0.001
SII
< 533.41	1 (Ref.)				1 (Ref.)
≥ 533.41	1.514 (1.035-2.217)	0.031			1.515 (1.035-2.217)	0.032
SIRI
< 1.51	1 (Ref.)				1 (Ref.)
≥ 1.51	1.899 (1.263-2.857)	0.002			1.881 (1.251-2.830)	0.002
Radical resection
Yes	1 (Ref.)		1 (Ref.)		1 (Ref.)		1 (Ref.)
No	4.356 (2.431-7.807)	< 0.001	1.909 (0.789-4.615)	0.151	4.182 (2.335-7.492)	< 0.001	1.513 (0.595-3.846)	0.384
Borrmann type
Ⅰ	1 (Ref.)		1 (Ref.)		1 (Ref.)		1 (Ref.)
Ⅱ	6.025 (1.435-25.300)	0.014	2.237 (0.477-10.497)	0.307	6.081 (1.448-25.533)	0.014	2.278 (0.484-10.729)	0.298
Ⅲ	8.012 (1.958-32.780)	0.004	2.350 (0.515-10.715)	0.270	8.088 (1.977-33.091)	0.004	2.435 (0.533-11.124)	0.251
Ⅳ	27.087 (6.171-118.891)	< 0.001	5.407 (1.063-27.496)	0.042	28.997 (6.605-127.294)	< 0.001	5.301 (1.043-26.930)	0.044
Lymph node positivity
No	1 (Ref.)		1 (Ref.)		1 (Ref.)		1 (Ref.)
Yes	3.445 (2.264-5.242)	< 0.001	1.132 (0.545-2.351)	0.740	3.537 (2.324-5.383)	< 0.001	1.010 (0.485-2.103)	0.979
Tumor size
< 20 mm	1 (Ref.)		1 (Ref.)		1 (Ref.)		1 (Ref.)
20–50 mm	2.710 (0.829-8.858)	0.099	0.708 (0.192-2.607)	0.603	2.715 (0.831-8.870)	0.098	0.686 (0.185-2.544)	0.573
> 50 mm	6.917 (2.176-21.988)	0.001	0.666 (0.178-2.494)	0.546	6.883 (2.165-21.878)	0.001	0.622 (0.164-2.361)	0.485
TNM stage
Ⅰ	1 (Ref.)		1 (Ref.)		1 (Ref.)		1 (Ref.)
Ⅱ	3.833 (1.585-7.910)	< 0.001	3.566 (1.545-8.233)	0.003	3.875 (1.878-7.996)	< 0.001	3.433 (1.475-7.989)	0.004
Ⅲ	11.441 (5.999-21.819)	< 0.001	9.085 (3.382-24.404)	< 0.001	11.807 (6.187-22.533)	< 0.001	8.541 (3.152-23.143)	< 0.001
Ⅳ	35.899 (15.895-81.079)	< 0.001	11.978 (3.812-37.641)	< 0.001	45.844 (20.022-104.969)	< 0.001	16.297 (4.934-53.825)	< 0.001
Carcinoembryonic antigen
< 1.97 ng/mL	1 (Ref.)		1 (Ref.)		1 (Ref.)		1 (Ref.)
≥ 1.97 ng/mL	1.586 (1.078-2.335)	0.019	1.425 (0.926-2.195)	0.107	1.543 (1.048-2.271)	0.028	1.328 (0.867-2.034)	0.192
CA199
< 10.19 U/L	1 (Ref.)				1 (Ref.)
≥ 10.19 U/L	1.355 (0.923-1.989)	0.120			1.347 (0.918-1.977)	0.128
CA724
< 2.17 U/L	1 (Ref.)		1 (Ref.)		1 (Ref.)		1 (Ref.)
≥ 2.17 U/L	2.159 (1.451-3.213)	< 0.001	1.510 (0.992-2.297)	0.054	2.154 (1.448-3.205)	< 0.001	1.456 (0.957-2.214)	0.079
CA125II
< 10.21 U/L	1 (Ref.)		1 (Ref.)		1 (Ref.)		1 (Ref.)
≥ 10.21 U/L	1.849 (1.250-2.734)	0.002	1.198 (0.791-1.813)	0.394	1.837 (1.242-2.716)	0.002	1.171 (0.770-1.781)	0.460
PII
< 70.69	1 (Ref.)		1 (Ref.)		1 (Ref.)		1 (Ref.)
≥ 70.69	1.888 (1.289-2.766)	0.001	1.670 (1.115-2.500)	0.013	1.881 (1.284-2.755)	0.001	1.639 (1.096-2.450)	0.016

CA125II: Carbohydrate antigen 125II; CA199: Carbohydrate antigen 199; CA724: Carbohydrate antigen 724; HR: Hazard ratio; NLR: Neutrophil-to-lymphocyte ratio; OS: Overall survival; PFS: Progression-free survival; PII: Prognostic immunoinflammatory index; PLR: Platelet-to-lymphocyte ratio; SII: Systemic immune inflammatory index; SIRI: Systemic inflammation response index; TNM: Tumor-node-metastasis.