The VEGFR-2 protein and the VEGFR-2 rs1870377 A>T genetic polymorphism are prognostic factors for gastric cancer

Figures & data

Table 1. Clinicopathological characteristics of these GC patients.

Characteristics	N = 256 (NO. of death ^a)	100%	Characteristics	N = 256 (NO. of death ^a)	100%
Sex			Depth of invasion
Male	165 (48)	64.45%	T1	123 (11)	48.05%
Female	91 (28)	35.55%	T2/T3/T4	133 (65)	51.95%
Age (year)			LNM
> 65	105 (40)	41.02%	N0	135 (17)	52.7%
≤ 65	151 (36)	58.98%	N1/N2/N3	121 (59)	47.3%
Smoking status			Distant metastasis
Yes	69 (17)	26.95%	M0	254 (72)	99.2%
No	187 (59)	73.05%	M1	2 (2)	0.8%
Drinking status			TNM stage
Yes	31 (10)	12.11%	I/II	175 (27)	68.4%
No	225 (66)	87.89%	III/IV	81 (49)	31.6%
Tumor size (cm)			Chemotherapy
> 4	75 (41)	29.30%	Yes	101 (36)	39.45%
≤ 4	181 (35)	70.70%	No	155 (40)	60.55%
Differentiation			VEGF
Well/Moderate	88 (18)	34.38%	VEGF (+)	45 (8)	17.58%
poor	168 (58)	65.62%	VEGF (-)	211 (68)	82.42%
Location			VEGFR-2
Cardia	18 (6)	7.03%	VEGFR-2 (++/+++)	135 (51)	52.73%
Non-cardia	238 (70)	92.97%	VEGFR-2 (+)	83 (20)	32.42%
			VEGFR-2 (-)	38 (5)	14.85%

^a Number of deaths were shown.

GC, gastric cancer; LNM, lymph node metastasis; VEGF, vascular endothelial growth factor;

VEGFR-2, vascular endothelial growth factor. receptor −2.

Table 2. Associations of genetic polymorphism of VEGFR-2 and survival of the GC patients.

SNP’s genes	Genotypes	Patients (N = 239)	Deaths (N = 107)	3-year survival rate	HR(95%CI) Univariate	P value	HR(95%CI) Univariate	P value	HR(95%CI) multivariate	P value^a	HR(95%CI) multivariate	P value^a
rs1870377	TT	48	21	63.8%	1.00(ref)		1.50(0.85–2.66)	0.161	1.00(ref)		1.69(0.95–3.02)	0.076
(T wild type)	AA	107	59	49.4%	1.38(0.84–2.26)	0.210	2.07(1.31–3.27)	0.002	1.00(0.60–1.66) 0.59(0.33–1.06) 1.00(ref)	0.990 0.076	1.69(1.06–2.68)	0.027
	AT	84	27	77.3%	0.67(0.38–1.18)	0.161	1.00(ref)				1.00(ref)
rs2071559	TT	114	49	65.6%	1.00(ref)		0.79(0.52–1.18)	0.249			0.71(0.47–1.07)	0.103
(T wild type)	CC	37	15	70.3%	0.87(0.49–1.54)	0.623	0.68(0.38–1.23)	0.301	1.11(0.62–1.99)	0.727	0.79(0.43–1.43)	0.304
	CT	88	43	54.1%	1.27(0.84–1.92)	0.249	1.00(ref)		1.41(0.93–2.14)	0.103	1.00(ref)
rs2305948	CC	184	85	60.6%	1.00(ref)		1.20(0.72–2.00)	0.478	1.00(ref)		1.24(0.74–2.08)	0.411
(C wild type)	TT	10	4	70.0% 5	0.81(0.30–2.22)	0.673	0.98(0.33–2.89)	0.966	1.03(0.37–2.84) 0.81(0.48–1.35) 1.00(ref)	0.960 0.411	1.27(0.42–3.82)	0.666
	TC	45	18	66.5%	0.83(0.50–1.38)	0.477	1.00(ref)				1.00(ref)
rs7667298	CC	102	46	62.6%	1.00(ref)		0.92(0.62–1.38)	0.697			0.77(0.51–1.17)	0.221
(C wild type)	TT	33	13	69.7%	0.80(0.43–1.47)	0.464	0.73(0.40–1.35)	0.321	0.87(0.47–1.62)	0.666	0.68(0.36–1.25)	0.214
	TC	104	48	59.2%	1.08(0.72–1.62)	0.697	1.00(ref)		1.29(0.86–1.95)	0.221	1.00(ref)

Abbreviations: HR, hazard ratio; CI, confidence interval.

^a Adjusted for size, differentiation, depth, TNM stage and smoking.

Figure 1. Kaplan-Meier survival curves of gastric cancer by VEGFR-2 rs1870377 A > T genetic polymorphism.

Figure 2. Immunohistochemistry results of VEGFR-2.

A1. Negative expression of VEGFR-2 in gastric cancer tissue. A2. Positive expression of VEGFR-2 in gastric cancer tissue.

Figure 3. Immunohistochemistry results of VEGF.

B1. Positive expression of VEGF in gastric cancer tissue. B2. Negative expression of VEGF in gastric cancer tissue.

Table 3. Comparison of the clinicopathological characteristics of GC patients of VEGF/VEGFR-2 expression.

Charateristics	VEGF (-) (%)	VEGF (+) (%)	P1-value	VEGFR-2(-) (%)	VEGFR-2(+) (%)	VEGFR-2(++/+++) (%)	P2-value
Sex			0.014				0.888
Male	129 (50.8%)	35 (13.8%)		26 (10.2%)	53 (20.9%)	85 (33.4%)
Female	82 (32.3%)	8 (3.1%)		12 (4.7%)	30(11.8%)	48 (18.9%)
Age(years)			0.088				0.299
>65	91 (35.8%)	12 (4.7%)		13 (5.1%)	30 (11.8%)	60 (23.6%)
≤ 65	120 (47.3%)	31 (12.2%)		25 (9.9%)	53 (20.9%)	73 (28.7%)
Location			0.500				0.133
cardia	13 (5.1%)	4 (1.6%)		3 (1.2%)	2 (0.8%)	12 (4.7%)
Non-cardia	198 (77.9%)	39 (15.4%)		35 (13.8%)	81 (31.9%)	121 (47.6%)
size(cm)			0.001				0.001
≤ 4	142 (55.9%)	39 (15.3%)		34 (13.4%)	64 (25.2%)	83 (32.6%)
>4	69 (27.2%)	4 (1.6%)		4 (1.6%)	19 (7.5%)	50 (19.7%)
Differentiation			0.861				0.001
Well/Moderate	73 (28.8%)	14 (5.5%)		23 (9.1%)	22 (8.7%)	42 (16.5%)
poor	138 (54.3%)	29 (11.4%)		15 (5.9%)	61 (24.0%)	91 (35.8%)
Depth of invasion			0.183				< 0.001
T1	98 (38.6%)	25 (9.8%)		30 (11.8%)	54 (21.3%)	39 (15.4%)
T2/T3/T4	113 (44.5%)	18 (7.1%)		8 (3.1%)	29 (11.4%)	94 (37.0%)
LNM			0.318				0.066
N0	109(42.9%)	26(10.2%)		25 (9.8%)	48 (18.9%)	62 (24.4%)
N1/N2/N3	102(40.2%)	17(6.7%)		13 (5.1%)	35 (13.8%)	71 (28.0%)
TNM stage			0.279				0.001
I/II	142(55.9%)	33(13.0%)		34(13.4%)	61(24.0%)	80(31.5%)
III	69(27.2%)	10(3.9%)		4(1.6%)	22(8.6%)	53(20.9%)
Smoking			0.256				0.622
Yes	53 (20.9%)	15 (5.9%)		11 (4.3%)	19 (7.5%)	38 (15.0%)
No	158 (62.2%)	28 (11.0%)		27 (10.6%)	64 (25.2%)	95 (37.4%)
Drinking			0.065				0.643
Yes	21 (8.3%)	9 (3.5%)		4 (1.6%)	12 (4.7%)	14 (5.5%)
No	190 (74.8%)	34 (13.4%)		34 (13.4%)	71 (28.0%)	119 (46.8%)

LNM, lymph node metastasis; VEGF, vascular endothelial growth factor; VEGFR-2, vascular endothelial growth factor receptor −2.

The cut point: VEGF, the product of intensity and percentage of positive cells > 6 was defined as positive, ≤ 6 was defined as negative.

VEGFR-2, the product of intensity and percentage of positive cells ≤ 1 was defined as negative;2-4was defined as weakly positive, ≥ 5 was defined as strongly.

positive.

Table 4. Associations of VEGF/VEGFR-2 expression and survival of the GC patients.

Variables	Patients (n = 254)	Overall survival rate (%)	3-year survival rate	HR(95%CI) Univariate	P1 value	HR(95%CI) multivariate	P2 value
VEGF
VEGF (-)	211	67.9%	74.4%	1.00(ref)		1.00(ref)
VEGF (+)	43	75.6%	78.7%	0.48(0.18–1.06)	0.069	0.53(0.23–1.25)	0.149
VEGFR-2
VEGFR-2 (-)	38	86.8%	92.1%	1.00(ref)		1.00(ref)
VEGFR-2 (+)	83	75.9%	80.1%	2.00(0.75–5.32)	0.167	1.33(0.48–3.67)	0.581
VEGFR-2 (++/+++)	133	63.2%	69.6%	3.00(1.19–7.52)	0.019	1.44(0.55–3.76)	0.455
Age(years)
≤ 65	151	76.2%	80.5%	1.00(ref)		1.00(ref)
>65	103	63.1%	68.8%	1.71(1.09–2.70)	0.021	1.53(0.96–2.44)	0.074
Size
≤ 4cm	181	80.7%	84.7%	1.00(ref)		1.00(ref)
>;4cm	73	46.6%	55.9%	3.37(2.13–5.32)	<0.001	1.44(0.87–2.40)	0.455
Differentiation
Well/Moderate	87	80.5%	84.5%	1.00(ref)		1.00(ref)
Poor	167	65.9%	72.0%	1.89(1.10–3.25)	0.021	1.22(0.69–2.15)	0.499
Depth of invasion
T1	123	91.1%	93.1%	1.00(ref)		1.00(ref)
T2/T3/T4	131	51.9%	61.1%	6.05(3.19–11.49)	<0.001	2.46(1.08–5.58)	0.031
LNM
N0	135	87.4%	89.8%	1.00(ref)		1.00(ref)
N1/N2/N3	119	52.1%	61.1%	4.37(2.54–7.52)	<0.001	1.87(0.84–4.16)	0.125
TNM stage
I/II	175	84.6%	88.0%	1.00(ref)		1.00(ref)
III	79	40.5%	50.6%	4.82(3.00–7.74)	<0.001	1.49(0.69–3.23)	0.309

Abbreviation: LNM, lymph node metastasis;

VEGFR-2(-), score ≤ 1, VEGFR-2(+), score2-4, VEGFR-2(++), score 5–8, VEGFR-2(+++),

score 9–12.

Figure 4. Kaplan-Meier survival curves of gastric cancer by VEGFR-2 status.