Baseline cytokines and programmed death-ligand 1 prognostic value in advanced gastric cancer with sintilimab plus chemotherapy

doi:10.3748/wjg.120447

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Oct 28, 2026; 32(40): 120447
Published online Oct 28, 2026. doi: 10.3748/wjg.120447

Table 1 Comparison of clinical data of patients, n (%)

Characteristic	Total (n = 101)
Age (year), median (IQR)	63 (54-71)
Sex
Male	54 (53.5)
Female	47 (46.5)
ECOG PS
0	38 (37.6)
1	63 (62.4)
Primary tumor site
Stomach	83 (82.2)
Gastroesophageal junction	18 (17.8)
Disease stage
Locally advanced	14 (13.9)
Metastatic	87 (86.1)
Chemotherapy regimen
Platinum-doublet (SOX/XELOX)	48 (47.5)
Taxane-based	53 (52.5)
BMI (kg/m²), median (IQR)	22.2 (19.6-23.2)
Tumor markers
AFP elevated	6 (5.9)
CEA elevated	51 (50.5)
CA19-9 elevated	51 (50.5)
CA12-5 elevated	12 (11.9)
CA72-4 elevated	62 (61.4)
Molecular markers
PD-L1 positive	80 (79.2)
EBV positive	8 (7.9)
dMMR	3 (3)
Cytokines (binary)
IL-4 high	41 (40.6)
IL-6 high	33 (32.7)
IL-8 high	62 (61.4)
IL-10 high	38 (37.6)
IL-17 high	51 (50.5)
Cytokines (pg/mL), median (IQR)
IL-4	0.32 (0.29-0.35)
IL-6	2.10 (2.05-2.15)
IL-8	14.20 (9.00-19.30)
IL-10	3.20 (2.30-4.40)
IL-17	3.30 (2.85-3.65)

IQR: Interquartile range; ECOG: Eastern Cooperative Oncology Group; PS: Performance status; SOX: Oxaliplatin + tegafur/gimeracil/oteracil; XELOX: Oxaliplatin + capecitabine; BMI: Body mass index; AFP: Alpha-fetoprotein; CEA: Carcinoembryonic antigen; CA: Carbohydrate antigen; PD-L1: Programmed death-ligand 1; EBV: Epstein-Barr virus; dMMR: Deficient mismatch repair; IL: Interleukin.

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Table 2 Receiver operating characteristic area under the curve for prediction of death in patients before immunotherapy by of cell factors

Index	AUC (95%CI)	Cut-off point	Sensitivity (%)	Specificity (%)
IL-4	0.678 (0.558-0.798)	0.34	95.0	53.7
IL-6	0.651 (0.540-0.762)	2.12	73.3	65.9
IL-8	0.667 (0.542-0.793)	9.09	94.2	51.3
IL-10	0.779 (0.665-0.894)	4.10	91.7	75.6
IL-17	0.654 (0.538-0.771)	3.03	97.6	39.0

AUC: Area under the curve; IL: Interleukin.

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Table 3 Comparison of cytokine distribution with different clinical characteristics, n (%)

Characteristic	IL-4			IL-6			IL-8			IL-10			IL-17
Characteristic	Low (n = 60)	High (n = 41)	P value	Low (n = 68)	High (n = 33)	P value	Low (n = 39)	High (n = 62)	P value	Low (n = 63)	High (n = 38)	P value	Low (n = 50)	High (n = 51)	P value
Age (year), median (Q₁, Q₃)	61.00 (52.00, 69.00)	66.00 (55.00, 71.00)	0.245	60.50 (51.75, 66.25)	66.00 (61.00, 79.00)	0.001	64.00 (54.00, 75.00)	61.50 (53.25, 69.00)	0.478	60.00 (50.50, 66.50)	66.00 (60.25, 75.50)	0.002	62.00 (54.00, 70.50)	65.00 (53.00, 70.00)	0.636
BMI (kg/m²), median (Q₁, Q₃)	21.63 (19.55, 22.90)	22.22 (20.31, 23.66)	0.225	21.79 (19.56, 23.18)	22.60 (20.31, 23.01)	0.498	22.22 (19.32, 23.18)	22.22 (20.11, 23.14)	0.485	22.22 (19.53, 23.18)	21.70 (20.31, 22.66)	0.872	21.70 (19.51, 22.76)	22.41 (19.83, 23.18)	0.392
ECOG			0.551			0.258			0.576			0.9			0.190
0	24 (40.00)	14 (34.15)		23 (33.82)	15 (45.45)		16 (41.03)	22 (35.48)		24 (38.10)	14 (36.84)		22 (44.00)	16 (31.37)
1	36 (60.00)	27 (65.85)		45 (66.18)	18 (54.55)		23 (58.97)	40 (64.52)		39 (61.90)	24 (63.16)		28 (56.00)	35 (68.63)
Sex			0.708			0.485			0.951			0.488			0.489
Male	33 (55.00)	21 (51.22)		38 (55.88)	16 (48.48)		21 (53.85)	33 (53.23)		32 (50.79)	22 (57.89)		25 (50.00)	29 (56.86)
Female	27 (45.00)	20 (48.78)		30 (44.12)	17 (51.52)		18 (46.15)	29 (46.77)		31 (49.21)	16 (42.11)		25 (50.00)	22 (43.14)
Tumor site			0.051			0.625			0.612			0.51			0.277
Stomach	53 (88.33)	30 (73.17)		55 (80.88)	28 (84.85)		33 (84.62)	50 (80.65)		53 (84.13)	30 (78.95)		39 (78.00)	44 (86.27)
Gastroesophageal junction	7 (11.67)	11 (26.83)		13 (19.12)	5 (15.15)		6 (15.38)	12 (19.35)		10 (15.87)	8 (21.05)		11 (22.00)	7 (13.73)
Stage			0.853			0.203			0.81			0.178			0.592
Local ate stage	8 (13.33)	6 (14.63)		12 (17.65)	2 (6.06)		5 (12.82)	9 (14.52)		11 (17.46)	3 (7.89)		6 (12.00)	8 (15.69)
Distant transfer	52 (86.67)	35 (85.37)		56 (82.35)	31 (93.94)		34 (87.18)	53 (85.48)		52 (82.54)	35 (92.11)		44 (88.00)	43 (84.31)
AFP			0.423			0.628			1			1			0.656
High	5 (8.33)	1 (2.44)		3 (4.41)	3 (9.09)		2 (5.13)	4 (6.45)		4 (6.35)	2 (5.26)		4 (8.00)	2 (3.92)
Normal	55 (91.67)	40 (97.56)		65 (95.59)	30 (90.91)		37 (94.87)	58 (93.55)		59 (93.65)	36 (94.74)		46 (92.00)	49 (96.08)
CEA			0.904			0.571			0.346			0.938			0.922
High	30 (50.00)	21 (51.22)		33 (48.53)	18 (54.55)		22 (56.41)	29 (46.77)		32 (50.79)	19 (50.00)		25 (50.00)	26 (50.98)
Normal	30 (50.00)	20 (48.78)		35 (51.47)	15 (45.45)		17 (43.59)	33 (53.23)		31 (49.21)	19 (50.00)		25 (50.00)	25 (49.02)
CA199			0.776			0.066			0.9			0.048			0.135
High	31 (51.67)	20 (48.78)		30 (44.12)	21 (63.64)		20 (51.28)	31 (50.00)		27 (42.86)	24 (63.16)		29 (58.00)	22 (43.14)
Normal	29 (48.33)	21 (51.22)		38 (55.88)	12 (36.36)		19 (48.72)	31 (50.00)		36 (57.14)	14 (36.84)		21 (42.00)	29 (56.86)
CA125			0.308			0.783			1			1			0.563
High	5 (8.33)	7 (17.07)		9 (13.24)	3 (9.09)		5 (12.82)	7 (11.29)		7 (11.11)	5 (13.16)		5 (10.00)	7 (13.73)
Normal	55 (91.67)	34 (82.93)		59 (86.76)	30 (90.91)		34 (87.18)	55 (88.71)		56 (88.89)	33 (86.84)		45 (90.00)	44 (86.27)
CA724			0.627			0.584			0.693			0.326			0.777
High	38 (63.33)	24 (58.54)		43 (63.24)	19 (57.58)		23 (58.97)	39 (62.90)		41 (65.08)	21 (55.26)		30 (60.00)	32 (62.75)
Normal	22 (36.67)	17 (41.46)		25 (36.76)	14 (42.42)		16 (41.03)	23 (37.10)		22 (34.92)	17 (44.74)		20 (40.00)	19 (37.25)
PD-L1			0.083			< 0.001			0.341			< 0.001			0.096
CPS < 5	9 (15.00)	12 (29.27)		4 (5.88)	17 (51.52)		10 (25.64)	11 (17.74)		4 (6.35)	17 (44.74)		7 (14.00)	14 (27.45)
CPS ≥ 5	51 (85.00)	29 (70.73)		64 (94.12)	16 (48.48)		29 (74.36)	51 (82.26)		59 (93.65)	21 (55.26)		43 (86.00)	37 (72.55)
EBV			1.000			1.000			0.229			0.709			0.282
No	55 (91.67)	38 (92.68)		63 (92.65)	30 (90.91)		38 (97.44)	55 (88.71)		59 (93.65)	34 (89.47)		48 (96.00)	45 (88.24)
Yes	5 (8.33)	3 (7.32)		5 (7.35)	3 (9.09)		1 (2.56)	7 (11.29)		4 (6.35)	4 (10.53)		2 (4.00)	6 (11.76)
MMR			0.599			0.859			0.333			0.484			1.000
pMMR	57 (95.00)	37 (90.24)		64 (94.12)	30 (90.91)		38 (97.44)	56 (90.32)		60 (95.24)	34 (89.47)		47 (94.00)	47 (92.16)
dMMR	3 (5.00)	4 (9.76)		4 (5.88)	3 (9.09)		1 (2.56)	6 (9.68)		3 (4.76)	4 (10.53)		3 (6.00)	4 (7.84)
Chemotherapy regimen			0.539			0.207			0.827			0.684			0.689
Platinum-doublet (SOX/XELOX)	27 (45.0)	21 (51.2)		30 (44.1)	10 (30.3)		18 (46.2)	30 (48.4)		31 (49.2)	17 (44.7)		25 (50.0%)	23 (45.1%)
Taxane- based	33 (55.0)	20 (48.8)		38 (55.9)	23 (69.7)		21 (53.8)	32 (51.6)		32 (50.8)	21 (55.3)		25 (50.0%)	28 (54.9%)

IL: Interleukin; BMI: Body mass index; ECOG: Eastern Cooperative Oncology Group; AFP: Alpha-fetoprotein; CEA: Carcinoembryonic antigen; CA: Carbohydrate antigen; PD-L1: Programmed death-ligand 1; CPS: Combined Positive Score; EBV: Epstein-Barr virus; MMR: Mismatch repair; dMMR: Deficient mismatch repair; pMMR: Proficient mismatch repair; SOX: Oxaliplatin + tegafur/gimeracil/oteracil; XELOX: Oxaliplatin + capecitabine.

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Table 4 Single factor Cox proportional hazards regression analysis of progression-free survival and overall survival

Variable	PFS		OS
Variable	HR (95%CI)	P value	HR (95%CI)	P value
Age (per year)	1.03 (1.01-1.05)	0.011	1.01 (0.99-1.03)	0.388
Sex (female vs male)	0.87 (0.56-1.35)	0.526	0.63 (0.37-1.08)	0.092
ECOG PS (1 vs 0)	0.89 (0.56-1.41)	0.623	1.04 (0.59-1.81)	0.899
Tumor site: GEJ vs gastric	1.21 (0.69-2.1)	0.505	0.89 (0.45-1.76)	0.734
Stage: Metastatic vs LA	1.18 (0.62-2.26)	0.607	0.8 (0.4-1.58)	0.516
Chemo: Taxane vs platinum	1.02 (0.65-1.58)	0.945	0.85 (0.51-1.43)	0.538
BMI (per unit)	1.02 (0.95-1.1)	0.543	0.99 (0.91-1.08)	0.832
AFP: Elevated vs normal	0.97 (0.39-2.4)	0.944	0.82 (0.29-2.28)	0.697
CEA: Elevated vs normal	1.16 (0.74-1.81)	0.512	1.14 (0.68-1.92)	0.609
CA199: Elevated vs normal	1.33 (0.85-2.08)	0.207	0.92 (0.55-1.55)	0.761
CA125: Elevated vs normal	0.8 (0.4-1.6)	0.526	1.02 (0.46-2.25)	0.965
CA724: Elevated vs normal	0.99 (0.64-1.55)	0.978	1.09 (0.64-1.84)	0.761
PD-L1: Positive vs negative	0.1 (0.05-0.19)	< 0.001	0.11 (0.05-0.25)	< 0.001
EBV: Positive vs negative	2.26 (1.08-4.75)	0.031	2.8 (1.17-6.69)	0.020
MMR: DMMR vs pMMR	2.49 (0.77-8.06)	0.127	1.93 (0.47-8.03)	0.364
IL-4: High vs low	1.36 (0.87-2.1)	0.174	1.06 (0.63-1.8)	0.814
IL-6: High vs low	8.12 (4.16-15.85)	< 0.001	7.32 (3.46-15.51)	< 0.001
IL-8: High vs low	1.14 (0.73-1.79)	0.555	1.55 (0.9-2.66)	0.112
IL-10: High vs low	10 (5.07-19.72)	< 0.001	8.26 (3.95-17.27)	< 0.001
IL-17: High vs low	3.72 (2.19-6.31)	< 0.001	5.8 (3.08-10.92)	< 0.001

PFS: Progression-free survival; OS: Overall survival; IL: Interleukin; ECOG: Eastern Cooperative Oncology Group; PS: Performance status; GEJ: Gastroesophageal junction; LA: Locally advanced; BMI: Body mass index; AFP: Alpha-fetoprotein; CEA: Carcinoembryonic antigen; CA: Carbohydrate antigen; PD-L1: Programmed death-ligand 1; EBV: Epstein-Barr virus; MMR: Mismatch repair; dMMR: Deficient mismatch repair; pMMR: Proficient mismatch repair.

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Table 5 Multivariable firth-penalized Cox regression for progression-free survival

Variable	HR (95%CI)	P value
IL-6: High vs low	3.82 (1.84-8.15)	< 0.001
IL-10: High vs low	4.38 (1.97-9.94)	< 0.001
IL-17: High vs low	1.94 (1.03-3.65)	0.041
Chemo regimen: Taxane vs platinum-doublet	1.13 (0.71-1.79)	0.605
PD-L1: Positive vs negative	0.35 (0.17-0.73)	0.006

IL: Interleukin; PD-L1: Programmed death-ligand 1.

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Table 6 Multivariable firth-penalized Cox regression for overall survival

Variable	HR (95%CI)	P value
IL-10: High vs low	3.35 (1.45-7.81)	0.005
IL-17: High vs low	3.94 (1.93-8.11)	< 0.001
Chemo regimen: Taxane vs platinum-doublet	0.87 (0.5-1.5)	0.623
PD-L1: Positive vs negative	0.32 (0.14-0.77)	0.012
EBV: Positive vs negative	2.9 (1.09-6.73)	0.034

IL: Interleukin; PD-L1: Programmed death-ligand 1; EBV: Epstein-Barr virus.

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Citation: Li YC, Pan D, Liu HN, Pei ZC, Li YQ, Han ZX, Liu WL. Baseline cytokines and programmed death-ligand 1 prognostic value in advanced gastric cancer with sintilimab plus chemotherapy. World J Gastroenterol 2026; 32(40): 120447
URL: https://www.wjgnet.com/1007-9327/full/v32/i40/120447.htm
DOI: https://dx.doi.org/10.3748/wjg.120447

Li YC, Pan D, Liu HN, Pei ZC, Li YQ, Han ZX, Liu WL. Baseline cytokines and programmed death-ligand 1 prognostic value in advanced gastric cancer with sintilimab plus chemotherapy. World J Gastroenterol 2026; 32(40): 120447 [DOI: 10.3748/wjg.120447]

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