ICAM2 loss drives 5-fluorouracil resistance via TGF-β/Smad/SP1/PTN-dependent apoptosis evasion and macrophage remodeling in gastric cancer

Table 1 Association between serum intercellular adhesion molecule 2 levels and clinicopathological features in advanced gastric cancer patients, n (%)

Variables	Cases	Low serum ICAM2 (n = 47)	High serum ICAM2 (n = 38)	P value
TRG-Ryan				< 0.001
0	16	2 (4)	14 (37)
1	11	1 (2)	10 (26)
2	43	33 (70)	10 (26)
3	15	11 (24)	4 (11)
Chemotherapy				< 0.001
Sensitive	27	3 (6)	24 (63)
Resistant	58	44 (94)	14 (37)
Age (years)				0.241
< 60	50	25 (53)	25 (66)
≥ 60	35	22 (47)	13 (34)
Sex				0.483
Male	64	34 (72)	30 (79)
Female	21	13 (28)	8 (21)
CEA (ng/mL)				0.271
≤ 5	61	36 (77)	25 (66)
> 5	24	11 (23)	13 (34)
CA19-9 (U/mL)				0.879
≤ 37	71	39 (83)	32 (84)
> 37	14	8 (17)	6 (16)
Tumor differentiation				0.008
High and moderate	36	14 (30)	22 (59)
Poor	47	32 (70)	15 (41)
Advanced TNM stage				0.041
II	41	18 (38)	23 (61)
III	44	29 (62)	15 (39)
Tumor location				0.613
Esophagogastric junction	23	12 (26)	11 (29)
Pylorus/corpus	29	18 (39)	11 (29)
Antrum	32	16 (35)	16 (42)

ICAM2: Intercellular adhesion molecule 2; TRG: Tumor regression grade; CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen.

Table 2 Univariate and multivariate analyses of factors associated with overall and disease-free survival in advanced gastric cancer patients

Variables	OS (univariate analysis)			OS (multivariate analysis)			DFS (univariate analysis)			DFS (multivariate analysis)
	HR	95%CI	P value	HR	95%CI	P value	HR	95%CI	P value	HR	95%CI	P value
ICAM2 in serum (high vs low)	0.378	0.202-0.707	0.002	0.441	0.234-0.828	0.011	0.403	0.222-0.730	0.003	0.446	0.245-0.811	0.008
Age (years; ≥ 60 vs < 60)	1.429	0.806-2.532	0.222				1.450	0.831-2.531	0.191
Gender (male vs female)	0.824	0.435-1.562	0.553				1.004	0.534-1.887	0.991
CEA (ng/mL; > 5 vs ≤ 5)	0.788	0.416-1.492	0.465				0.660	0.351-1.242	0.198
CA19-9 (U/mL; > 37 vs ≤ 37)	1.954	0.995-3.838	0.052				1.751	0.896-3.421	0.101
Differentiation (high and moderate vs poor)	0.588	0.323-1.067	0.081				0.688	0.388-1.221	0.201
Advanced TNM stage (III vs II)	3.298	1.763-6.170	< 0.001	2.938	1.562-5.528	0.001	3.226	1.776-5.860	< 0.001	2.977	1.644-5.462	< 0.001

OD: Overall survival; DFS: Disease-free survival; ICAM2: Intercellular adhesion molecule 2; CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen.