Increased BTLA and HVEM in gastric cancer are associated with progression and poor prognosis

Figures & data

Figure 1 Representative picture of immunohistochemical staining of BTLA and HVEM in gastric tissues.

Notes: (A) Negative BTLA expression in adjacent normal specimen. (B) Low BTLA expression in gastric cancer. (C) High BTLA expression in gastric cancer. (D) Negative HVEM expression in adjacent normal specimen. (E) Low HVEM expression in gastric cancer. (F) High HVEM expression in gastric cancer. Magnifications: ×400.
Abbreviations: BTLA, B- and T-lymphocyte attenuator; HVEM, herpesvirus entry mediator.

Table 1 Association between BTLA and HVEM expression and clinicopathological factors of gastric cancer patients

Variable	Case N	BTLA			HVEM
		Low N (%)	High N (%)	P-valuesa	Low N (%)	High N (%)	P-valuesa
Age, years				0.842			0.269
<60	74	54 (73.0)	20 (27.0)		44 (59.5)	30 (40.5)
≥61	62	43 (69.4)	19 (30.6)		31 (50.0)	31 (50.0)
Gender				0.642			0.545
Male	95	69 (72.6)	26 (27.4)		54 (56.8)	41 (43.2)
Female	41	28 (68.3)	13 (31.7)		21 (51.2)	20 (48.8)
Tumor size, cm				0.244			0.141
<5	63	48 (76.2)	15 (23.8)		39 (61.9)	24 (38.1)
≥5	73	49 (67.1)	24 (32.9)		36 (49.3)	37 (50.7)
Location				0.458			0.163
Upper third	16	13 (81.2)	3 (18.8)		8 (50.0)	8 (50.0)
Middle third	37	24 (64.9)	13 (35.1)		16 (43.2)	21 (56.8)
Lower third	83	60 (72.3)	23 (27.7)		51 (61.4)	32 (38.6)
Borrmann type				0.221			0.053
I/II	38	30 (78.9)	8 (21.1)		26 (68.4)	12 (31.6)
III/IV	98	67 (68.4)	31 (31.6)		49 (50.0)	49 (50.0)
Depth of invasion				0.284			0.011
T1–2	29	23 (79.3)	6 (20.7)		22 (75.9)	7 (24.1)
T3–4	107	74 (69.2)	33 (30.8)		53 (49.5)	54 (50.5)
Lymph node metastasis				0.030			0.007
No	43	36 (83.7)	7 (16.3)		31 (72.1)	12 (27.9)
Yes	93	61 (65.6)	32 (34.4)		44 (47.3)	49 (52.7)
Histological grade				0.556			0.695
Well/moderate	47	35 (74.5)	12 (25.5)		27 (57.4)	20 (42.6)
Poor	89	62 (69.7)	27 (30.3)		48 (53.9)	41 (46.1)

Note:

a χ² test.

Abbreviations: BTLA, B- and T-lymphocyte attenuator; HVEM, herpesvirus entry mediator.

Table 2 Relationship between BTLA and HVEM expression in gastric cancer

BTLA	HVEM			r-value	P-valuea
	High	Low	Total
High	25	14	39	0.245	0.004
Low	36	61	97
Total	61	75

Note:

a Spearman’s rank.

Abbreviations: BTLA, B- and T-lymphocyte attenuator; HVEM, herpesvirus entry mediator.

Figure 2 Kaplan–Meier curves of OS based on BTLA expression in patients with gastric cancer.

Notes: Higher expression of BTLA was closely correlated with poor OS (P=0.001).
Abbreviations: OS, overall survival; BTLA, B- and T-lymphocyte attenuator; Cum, cumulative.

Figure 3 Kaplan–Meier curves of OS based on HVEM expression in patients with gastric cancer.

Notes: Higher expression of HVEM was closely correlated with poor OS (P<0.001).
Abbreviations: OS, overall survial; HVEM, herpesvirus entry mediator; Cum, cumulative.

Table 3 Univariate and multivariate analysis of the prognostic factors in 136 patients with gastric cancer

Variable	Univariate		Multivariate
	Mean survival (months) (95% CI)	P-valuesa	HR (95% CI)	P-valuesb
Age, years		0.694
<60	45.770 (39.861–51.679)
≥61	44.512 (37.794–51.230)
Gender		0.559
Male	46.116 (40.664–51.568)
Female	42.755 (35.346–50.164)
Tumor size, cm		0.031
<5	49.748 (43.019–56.477)
≥5	41.216 (35.496–46.935)
Location		0.256
Upper third	50.035 (36.890–63.179)
Middle third	39.541 (31.480–47.601)
Lower third	46.682 (40.915–49.869)
Borrmann type		0.018
I/II	52.632 (44.091–61.172)
III/IV	42.359 (37.265–47.453)
Depth of invasion		<0.001		0.001
T1–2	67.932 (61.230–74.635)		1 ref
T3–4	39.001 (34.301–43.700)		2.281 (1.418–3.671)
Lymph node metastasis		<0.001		<0.001
No	66.450 (61.032–71.868)		1 ref
Yes	35.442 (30.598–40.286)		1.499 (1.200–1.874)
Histological grade		0.013		0.027
Well/moderate	53.160 (45.886–60.434)		1 ref
Poor	41.031 (35.634–46.428)		1.334 (1.033–1.723)
BTLA expression		0.001
Low	49.537 (44.191–54.883)
High	34.987 (27.835–42.139)
HVEM expression		<0.001		0.010
Low	54.972 (49.226–60.718)		1 ref
High	33.354 (27.630–39.077)		1.857 (1.161–2.970)

Notes:

a Log-rank test;

b Cox regression test.

Abbreviations: BTLA, B- and T-lymphocyte attenuator; CI, confidence interval; HR, hazard ratio; HVEM, herpesvirus entry mediator; ref, reference.