Clinical significance of programmed death 1/programmed death ligand 1 pathway in gastric neuroendocrine carcinomas

Table 1 Clinical characteristics of 43 patients with gastric neuroendocrine carcinomas

Clinicopathological feature	n (%)
Age (yr)
< 60/≥ 60	15 (34.88)/28 (65.12)
mean ± SD	62.26 ± 10.46
Gender
Male/female	35 (81.40)/8 (18.60)
Tumor location
Cardia	21 (48.84)
Corpus	10 (23.26)
Antrum	10 (23.26)
Residual stomach anastomosis	2 (4.65)
Tumor size (max diameter, cm)
≤ 5/> 5	20 (46.51)/23 (53.49)
mean ± SD	5.47 ± 3.18
T classification
T1/T2/T3/T4	0 (0)/4 (9.30)/0 (0)/39 (90.70)
Lymph node metastasis
N0/N1	12 (27.91)/31 (72.09)
Liver metastasis
Absent/present	37 (86.05)/6 (13.95)
Pathological stage
I/II/III/IV	0 (0)/2 (4.65)/35 (81.40)/6 (13.95)
Pathology
Small cell carcinomas	39 (90.70)
Large cell carcinomas	4 (9.30)
Operation
Curative resection	38 (88.37)
Palliative resection	5 (11.63)
Neoadjuvant therapy
No/present	100 (100)/0 (0)
Follow-up
Median OS (mo)	31.0

Patients were staged in accordance with the 7th Edition of the AJCC Cancer TNM Classification. OS: Overall survival.

Table 2 Relationship between clinical characteristics and immune markers

	Low CD8 n (%)	High CD8 n (%)	P-value	Low FOXP3 n (%)	High FOXP3 n (%)	P-value	Low PD-1 n (%)		High PD-1 n (%)	P-value	Low PD-L1 n (%)	High PD-L1 n (%)	P-value
Age (yr)
< 60	7	8	0.835	11	4	0.019	9		6	0.284	7	8	0.666
≥ 60	14	14		10	18		12		16		15	13
Gender
Male	17	18	0.942	14	21	0.015		16	19	0.391	19	16	0.391
Female	4	4		7	1			5	3		3	5
Tumor location
Cardia	9	12	0.492	11	10	0.018		10	11	0.999	11	10	0.489
Corpus	7	3		1	9			5	5		5	5
Antrum	4	6		7	3			5	5		4	6
Residual stomach anastomosis	1	1		2	0			1	1		2	0
Tumor size
≤ 5 cm	12	8	0.172	11	9	0.451		11	9	0.451	10	10	0.887
> 5 cm	9	14		10	13			10	13		12	11
T classification
T1/2	3	1	0.272	2	2	0.961		2	2	0.961	1	3	0.272
T3/4	18	21		19	20			19	20		21	18
Lymph node metastasis
≤ 7	5	7	0.558	3	9	0.052		5	7	0.558	6	6	0.924
> 7	16	15		18	13			16	15		16	15
Liver metastasis
Absent	17	20	0.346	18	19	0.951		16	21	0.068	19	18	0.951
Present	4	2		3	3			5	1		3	3
CD8
High
Low
FOXP3
Low	9	12	0.443
Hight	12	10
PD-1
Low	13	8	0.094	12	9	0.287
High	8	14		9	13
PD-L1
Low	9	13	0.287	12	10	0.443		15	7	0.009
High	12	9		9	12			6	15

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

Table 3 Univariate and multivariate analyses of prognostic parameters for survival in the cohort patients with gastric neuroendocrine carcinomas

Prognostic parameter	Univariate			Multivariate
	HR	95%CI	P-value	HR	95%CI	P-value
Age (yr)
< 60	1.0 (Reference)
≥ 60	2.718	0.921-8.023	0.07
Gender
Male	1.0 (Reference)
Female	0.915	0.308-2.718	0.873
Tumor location
Cardia	1.0 (Reference)
Corpus	3.034	1.100-8.374	0.032	2.878	0.971-8.529	0.057
Antrum	2.331	0.817-6.648	0.114	2.51	0.285-22.125	0.407
Residual stomach anastomosis	1.401	0.176-11.159	0.75	1.373	0.399-4.718	0.615
Tumor size
≤ 5 cm	1.0 (Reference)
> 5 cm	1.605	0.693-3.717	0.269
T classification
T1/2	1.0 (Reference)
T3/4	0.76	0.407-1.420	0.39
Lymph node metastasis
Absent	1.0 (Reference)
Present	1.976	0.731-5.342	0.179
Liver metastasis
Absent	1.0 (Reference)
Present	3.515	1.269-9.731	0.016	4.045	1.140-14.351	0.031
CD8
Low	1.0 (Reference)
High	0.46	0.197-1.074	0.073
FOXP3
Low	1.0 (Reference)
High	1.375	0.593-3.186	0.458
PD-1
Low	1.0 (Reference)
High	0.954	0.420-2.167	0.91
PD-L1
Low	1.0 (Reference)
High	2.846	1.170-6.922	0.021	3.646	1.372-9.688	0.009

PD-L1: Programmed death ligand 1; PD-1: Programmed death 1. HR: Hazard ratio; CI: Confidence interval.