Tumor expression of B7-H4 predicts poor survival of patients suffering from gastric cancer

Abstract

To establish the prognostic value of B7-H4 expression by tumor cells in gastric cancer patients, we evaluated the association of B7-H4 expression with clinicopathologic factors and overall survival of gastric cancer patients. A retrospective cohort study including 156 gastric cancer patients was performed in the present report. Immunohistochemical assay was used to evaluate the expression of B7-H4 in the surgical specimens of gastric cancer tissues. Multi-univariate COX model was then used to evaluate the association of B7-H4 expression with the patients' survival and clinicopathological parameters. B7-H4 expression in the gastric cancer cells was observed in about 44.9% gastric cancer specimens. Univariate analysis demonstrated that there was no correlation between B7-H4 expression and sex, age, histological type, pathological grade or tumor size. In contrast, B7-H4 expression correlated positively with cancer invasiveness and lymph node metastasis. In addition, the median overall survival time of patients with lower B7-H4 expression was 13 months longer than that of patients with higher expression (chi(2) = 12.38, P < 0.0001), and the median disease-free survival time of patients with lower B7-H4 expression was significantly longer than that of patients with higher expression (33 vs. 16 months, chi(2) = 14.977, P < 0.0001). After adjustment for other confounding factors, the COX model analysis indicated that the death risk was significantly higher in patients with higher B7-H4 expression than those with lower expression (RR = 1.85, 95% CI = 1.15-2.96). The present study demonstrated that higher B7-H4 expression in cancer cells was associated with poor prognosis of gastric cancer patients. This is consistent with the idea that B7-H4 promotes cancer progression, likely via inhibition of anti-tumor immune responses.

Fig. 1

Immunohistochemical staining of B7-H4. The B7-H4 immunohistochemical staining in gastric cancer (a, higher expression; b, lower expression), gastritis (c) and gastric polyp tissues (d) is shown. Left panels show HE staining. Middle and right panels show B7-H4 staining at lower and higher magnifications, respectively

Fig. 2

Differential B7-H4 expression in the gastric cancer tissue (higher and lower expression), gastritis and gastric polyp tissues. Intensity of expression of B7-H4 was evaluated according to the immunohistochemical score as described in “Materials and methods”. *p < 0.05; **p < 0.001

Fig. 3

Overall survival of gastric cancer patients with different levels of B7-H4 expression. a All patients were divided into higher and lower B7-H4 expression groups. Survival data were analyzed by Kaplan–Meier method and log-rank test. b Patients in stages I and II were divided into higher and lower B7-H4 expression groups and survival data were analyzed by Kaplan–Meier method and log-rank test. Patients in stages III and IV were also divided into higher and lower B7-H4 expression groups and survival data were analyzed by Kaplan–Meier method and log-rank test

Fig. 4

Disease-free survival curve of gastric cancer patients with lower and higher B7-H4 expression. The median disease-free survival time of patients with lower B7-H4 expression was significantly longer than that of patients with higher B7-H4 expression (33 vs. 16 months, χ² = 14.977, P < 0.0001)