Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression

Table 1 Heparanase and mitogen-activated protein kinase expression in specimens of gastric cancer n (%)

	Cases (n)	Immunohistochemical result				HR (P value)
		-	+	++	+++
HPA
Gastric cancer	99	30 (30.3)	16 (16.2)	25 (25.3)	28 (28.3)	35.547 (0.000)
Para-cancer	99	57 (57.6)	11 (11.1)	17 (17.2)	16 (16.2)b
Normal tissue	25	24 (96.0)	1 (4.0)	0 (0.0)	0 (0.0)bd
MAPK
Gastric cancer	99	49 (49.5)	12 (12.1)	19 (19.2)	19 (19.2)	33.303 (0.000)
Para-cancer	99	82 (82.8)	5 (5.1)	6 (6.1)	6 (6.1)b
Normal tissue	25	23 (92.0)	2 (8.0)	0 (0.0)	0 (0.0)b

P values < 0.05 were determined using one way analysis of variance (ANOVA):

^bP: Comparison with gastric cancer;

^dP: Comparison with para-cancer tissue. HPA: Heparanase; MAPK: Mitogen-activated protein kinase; HR: Hazard ratio.

Table 2 Correlation between Helicobacter pylori infection and gastric cancer n (%)

H. pylori infection	Gastric cancer (n = 99)	Normal tissue (n = 25)	χ2	P value	C
Negative	29 (29.29)	15 (60.00)	8.221	0.004	0.229
Positive	70 (70.71)	10 (40.00)

H. pylori: Helicobacter pylori.

Table 3 Correlation analyses of Helicobacter pylori infection, heparanase and mitogen-activated protein kinase expression, and gastric cancer pathological characteristics n (%)

Parameter	Cases (n)	H. pylori infection		P value	HPA expression		P value	MAPK expression		P value
		Positive	Negative		Positive	Negative		Positive	Negative
Age (yr)
< 60	46	32 (32.3)	14 (14.1)	0.816	31 (31.3)	14 (14.1)	0.8731	22 (22.2)	24 (24.2)	0.619
≥ 60	53	38 (38.4)	15 (15.2)		38 (38.4)	16 (16.2)		28 (28.3)	25 (25.3)
Gender
Male	61	46 (46.5)	15 (15.2)	0.193	42 (42.4)	18 (18.2)	0.935	27 (27.3)	34 (34.3)	0.115
Female	38	24 (24.2)	14 (14.1)		27 (27.3)	12 (12.1)		23 (23.2)	15 (15.2)
Lymph node metastasis
Without	42	24 (24.2)	18 (18.2)	0.011	23 (23.2)	19 (19.2)	0.006	24 (24.2)	18 (18.2)	0.257
With	57	46 (46.5)	11 (11.1)		46 (46.5)	11 (11.1)		26 (26.3)	31 (31.3)
Tumour diameter
< 40 mm	57	40 (40.4)	17 (17.2)	0.892	39 (39.4)	17 (17.2)	0.989	25 (25.3)	32 (32.3)	0.123
≥ 40 mm	42	30 (30.3)	12 (12.1)		30 (30.3)	13 (13.1)		25 (25.3)	17 (17.2)
Differentiation degree
Poorly	40	28 (28.3)	12 (12.1)	0.899	26 (26.3)	14 (14.1)	0.402	23 (23.2)	17 (17.2)	0.252
Highly and moderately	59	42 (42.4)	17 (17.2)		43 (43.3)	16 (16.2)		27 (27.3)	32 (32.3)
Invasive depth
T1/2	39	31 (31.3)	8 (8.1)	0.122	33 (33.3)	6 (6.1)	0.009	24 (24.2)	15 (15.2)	0.077
T3/4	60	39 (39.4)	21 (21.2)		36 (36.4)	24 (24.2)		26 (26.3)	34 (34.3)

HPA: Heparanase; MAPK: Mitogen-activated protein kinase; H. pylori: Helicobacter pylori.

Table 4 Correlation between heparanase expression and Helicobacter pylori infection in gastric cancer

H. pylori infection	HPA expression		χ2	P value	C
	Negative	Positive
Negative	14 (14.1)	15 (15.2)	6.273	0.012	0.244
Positive	16 (16.2)	54 (54.5)

HPA: Heparanase; H. pylori: Helicobacter pylori.

Table 5 Correlation between mitogen-activated protein kinase expression and Helicobacter pylori infection in gastric cancer

H. pylori infection	MAPK expression		χ2	P value	C
	Negative	Positive
Negative	19 (19.2)	10 (10.1)	4.212	0.04	0.202
Positive	30 (30.3)	40 (40.4)

MAPK: Mitogen-activated protein kinase; H. pylori: Helicobacter pylori.

Table 6 Correlation between heparanase expression and mitogen-activated protein kinase expression in gastric cancer

HPA expression	MAPK expression		χ2	P value	C
	Negative	Positive
Negative	20 (19.2)	10 (11.1)	5.077	0.024	0.221
Positive	29 (30.3)	40 (39.4)

HPA: Heparanase; MAPK: Mitogen-activated protein kinase.

Table 7 Univariate COX regression analysis

Variable	Overall survival
	HR	95%CI	P value
Gender (man vs women)	0.952	0.498-1.821	0.882
Age (≥ 60 vs < 60)	1.113	0.581-2.130	0.747
Tumour diameter (≥ 40 mm vs < 40 mm)	1.285	0.684-2.413	0.436
Lymph metastasis (yes vs no)	2.667	1.381-5.128	0.003
Tissue differentiation (high and medium vs low)	4.156	1.622-10.656	0.003
Invasive depth (T3/4 vs T1/2)	2.464	1.189-5.104	0.015
HPA expression (positive vs negative)	3.282	1.968-7.475	0.000
MARK expression (positive vs negative)	2.083	1.068-4.065	0.031
H. pylori (positive vs negative)	1.065	0.556-2.045	0.849

HPA: Heparanase; MAPK: Mitogen-activated protein kinase; H. pylori: Helicobacter pylori; HR: Hazard ratio; CI: Confidence interval.

Table 8 Multivariate COX regression analysis

Variable	Overall survival
	HR	95%CI	P value
Lymph metastasis (yes vs no)	4.443	2.185-9.036	0.000
Tissue differentiation (high and medium vs low)	3.452	1.299-9.176	0.013
Invasive depth (T3/4 vs T1/2)	2.542	1.198-5.392	0.015
HPA expression (positive vs negative)	2.463	1.195-5.076	0.015

HPA: Heparanase; HR: Hazard ratio; CI: Confidence interval.