High PD-L1 expression as a negative prognostic factor in stage III but not in stage II gastric cancer

Table 1 Baseline patient characteristics

Variables	Cases	Total
Sex		388
Male	249 (64.2)
Female	139 (35.8)
Age (year)	58.05 ± 12.61
Tumor size (cm)		387
< 5	266 (68.7)
≥ 5	121 (31.3)
Lesion sites		386
Stomach	294 (76.2)
GEJ	92 (23.8)
Histology		385
Sig	141 (36.6)
Others	244 (63.4)
Grade		381
G1-G2	80 (21.0)
G3	301 (79.0)
Pathological stage		388
pII	159 (41.0)
pIIIA	99 (25.5)
pIIIB	84 (21.6)
pIIIC	46 (11.9)
Postoperative adjuvant chemotherapy		388
Yes	229 (59.0)
No	159 (41.0)
HER-2 expression		369
Negative	337 (91.3)
Positive	32 (8.7)
MMR status		368
dMMR	20 (5.4)
pMMR	348 (94.6)
EBV status		376
Negative	360 (95.7)
Positive	16 (4.3)
PD-L1 CPS		388
Negative (< 1)	126 (32.5)
Positive (≥ 1)	262 (67.5)
pII		159
Negative (< 1)	52 (32.7)
Positive (≥ 1)	107 (67.3)
pIII		229
Negative (< 1)	74 (32.3)
Positive (≥ 1)	155 (67.7)
PD-L1 CPS		388
Low expression (< 5)	187 (48.2)
High expression (≥ 5)	201 (51.8)
pII		159
Low expression (< 5)	74 (46.5)
High expression (≥ 5)	85 (53.5)
pIII		229
Low expression (< 5)	113 (49.3)
High expression (≥ 5)	116 (50.7)
Ki-67 index	59.31 ± 23.04

Data were shown as n (%) or mean ± SD. GEJ: Gastroesophageal junction; Sig: Signet ring cell carcinoma; pII: Pathological stage II; pIII: Pathological stage III; MMR: Mismatch repair; dMMR: Deficient mismatch repair; pMMR: Proficient mismatch repair; EBV: Epstein-Barr virus; PD-L1: Programmed death ligand-1; CPS: Combined positive score.

Table 2 Clinicopathological features associated with high programmed death ligand-1 expression group in pathological stage III gastric or gastroesophageal junction cancer

Variables	High PD-L1 expression (n = 116)	Low PD-L1 expression (n = 113)	Statistic	P value
Sex			1.914	0.167
Male	78 (67.2)	66 (58.4)
Female	38 (32.8)	47 (41.6)
Age (year)	59.51 ± 12.05	55.41 ± 13.31	-2.445	0.015
Tumor size (cm)			0.002	0.964
< 5	76 (66.1)	75 (66.4)
≥ 5	39 (33.9)	38 (33.6)
Lesion sites			3.194	0.074
Stomach	79 (69.3)	90 (79.6)
GEJ	35 (30.7)	23 (20.4)
Histology			4.007	0.045
Sig	40 (35.1)	54 (48.2)
Others	74 (64.9)	58 (51.8)
Grade			0.888	0.346
G1-G2	19 (17.0)	14 (12.5)
G3	93 (83.0)	98 (87.5)
Pathological stage			1.263	0.532
pIIIA	51 (44.0)	48 (42.5)
pIIIB	39 (33.6)	45 (39.8)
pIIIC	26 (22.4)	20 (17.7)
HER-2 expression			0.728	0.394
Negative	100 (89.3)	100 (92.6)
Positive	12 (10.7)	8 (7.4)
MMR status			0.000	1.000
dMMR	5 (4.3)	4 (3.5)
pMMR	111 (95.7)	109 (96.5)
EBV status			1.779	0.182
Negative	105 (93.8)	108 (98.2)
Positive	7 (6.3)	2 (1.8)
Ki-67 index	63.78 ± 22.09	55.36 ± 23.28	-2.795	0.006
Postoperative adjuvant chemotherapy			0.929	0.335
Yes	72 (62.1)	77 (68.1)
No	44 (37.9)	36 (31.9)

Data were shown as n (%) or mean ± SD. GEJ: Gastroesophageal junction; Sig: Signet ring cell carcinoma; pIII: Pathological stage III; MMR: Mismatch repair; dMMR: Deficient mismatch repair; pMMR: Proficient mismatch repair; EBV: Epstein-Barr virus; PD-L1: Programmed death ligand-1.

Table 3 Univariate and multivariate analyses of clinicopathological features associated with disease-free survival and overall survival for pathological stage III gastric or gastroesophageal junction cancer

Variables	DFS-univariate		DFS-multivariate		OS-univariate		OS-multivariate
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Sex
Male	1.000				1.000
Female	1.101 (0.725, 1.670)	0.652			1.067 (0.670, 1.702)	0.784
Age (year)
< 65	1.000				1.000
≥ 65	1.249 (0.810, 1.926)	0.314			1.782 (0.772, 4.112)	0.176
Tumor size (cm)
< 5	1.000				1.000
≥ 5	1.143 (0.743, 1.759)	0.542			1.394 (0.869, 2.238)	0.169
Lesion sites
Stomach	1.000				1.000
GEJ	1.228 (0.778, 1.938)	0.377			1.058 (0.631, 1.772)	0.831
Histology
Other	1.000				1.000
Sig	0.900 (0.590, 1.373)	0.626			0.962 (0.602, 1.537)	0.870
Grade
G1-G2	1.000				1.000
G3	0.873 (0.501, 1.520)	0.631			0.755 (0.414, 1.380)	0.362
Pathological stage
pIIIA	1.000	< 0.001	1.000	< 0.001	1.000	< 0.001	1.000	< 0.001
pIIIB	1.716 (1.030, 2.861)	0.038	1.719 (1.018, 2.903)	0.043	1.953 (1.080, 3.533)	0.027	1.897 (1.026, 3.509)	0.041
pIIIC	3.584 (2.130, 6.029)	< 0.001	3.423 (2.012, 5.822)	< 0.001	4.269 (2.348, 7.761)	< 0.001	4.237 (2.291, 7.837)	< 0.001
HER-2 expression
Negative	1.000		1.000		1.000		1.000
Positive	1.798 (0.977, 3.308)	0.059	1.680 (0.910, 3.100)	0.097	1.332 (0.660, 2.689)	0.423	1.148 (0.566, 2.328)	0.702
MMR status
dMMR	1.000				1.000
pMMR	0.505 (0.221, 1.156)	0.106			0.475 (0.191, 1.178)	0.108
EBV status
Negative	1.000				1.000
Positive	0.671 (0.212, 2.123)	0.497			0.555 (0.136, 2.266)	0.412
PD-L1 expression
Low	1.000		1.000		1.000		1.000
High	1.608 (1.060, 2.438)	0.026	1.624 (1.056, 2.500)	0.027	1.639 (1.026, 2.619)	0.039	1.653 (1.016, 2.688)	0.043

DFS: Disease-free survival; OS: Overall survival; GEJ: Gastroesophageal junction; Sig: Signet ring cell carcinoma; pIII: Pathological stage III; MMR: Mismatch repair; dMMR: Deficient mismatch repair; pMMR: Proficient mismatch repair; EBV: Epstein-Barr virus; PD-L1: Programmed death ligand-1.