Serum B7-H4 expression is a significant prognostic indicator for patients with gastric cancer

Abstract

BackgroundB7-H4 is a novel B7 ligand that plays an important role in the T cell-mediated immune response as a negative regulator. Previous studies have suggested the aberrant expression of membrane B7-H4 in tumor cells. The aim of this study is to determine the expression levels of preoperative soluble B7-H4 (sB7-H4) in circulation and to investigate the correlations between sB7-H4 levels and clinicopathological parameters as well as the survival rate of patients with gastric cancer.MethodsBlood specimens from 132 patients with gastric cancer and 63 healthy volunteers were analyzed by sandwich enzyme-linked immunosorbent assay.ResultsMedian concentrations of sB7-H4 in patients with gastric cancer were significantly higher than those in healthy volunteers (16.85 versus 10.46 ng/mL; P = 0.008). Median levels of sB7-H4 were significantly correlated with tumor size, lymph node metastasis, the depth of tumor invasion and tumor-node-metastasis classification (P = 0.002, P = 0.001, P = 0.041 and P <0.001, respectively), but not with sex, age, tumor location or histological subtype (all P >0.05). Additionally, the overall survival rate was significantly lower in patients with high sB7-H4 levels when compared with low sB7-H4 levels (50.0% versus 77.3%, χ2 = 10.78, P = 0.001). Moreover, multivariate analysis demonstrated that the risk of death was significantly higher in patients with high sB7-H4 levels than in those with low sB7-H4 levels (P = 0.039).ConclusionssB7-H4 is a valuable blood marker for predicting the progression and prognosis of patients with gastric cancer.

Diagnostic value of serum B7-H4 for hepatocellular carcinoma

“…Thompson et al [22] found that sB7-H4 levels in renal cell cancer patients were significantly higher than those in normal controls. Shi et al [21] reported that sB7-H4 levels were significantly increased in patients with gastric cancer compared with the level of sB7-H4 in healthy volunteers. Liu et al [17] showed that, compared with the healthy control group, the sB7-H4 concentrations in patients with bladder urothelial carcinoma were also significantly increased.…”

“…The levels of circulating sB7-H4 in the serum were measured by ELISA as previously described [19,21]. Briefly, 25 mL of the undiluted serum sample was added to high-binding polystyrene plates coated with capture mAb (Clone H74; eBioscience, San Diego, CA).…”

“…In addition, the status of B7-H4 expression in tumor cells of these malignancies is closely associated with progression and prognosis [18]. Recently, soluble B7-H4 (sB7-H4) has been detected in blood samples from various cancer patients, including ovarian [19,20], gastric [21], renal cell carcinoma [22], and bladder urothelial carcinoma [17], and high levels of sB7-H4 were a significant prognostic indicator [21].…”

Circulating B7-H4 in serum predicts prognosis in patients with hepatocellular carcinoma

“…Simon and his colleagues found that the expression level of serum B7-H4 was significant higher in patients with ovarian cancer as compared with healthy controls (Simon et al, 2006). Recently, higher serum B7-H4 level was also reported in gastric cancer patients, and was closely correlated with many important clinic-pathological parameters of gastric cancer, further supporting its potential value for early diagnosis and prediction of disease prognosis (Shi et al, 2014).…”

“…In agreement with this, Oikonomopoulou et al (2008) reported that serum B7-H4 may be a promising biomarker for prediction of ovarian cancer prognosis and chemotherapy response. Recently, Shi et al (2014) found that serum B7-H4 expression level was significantly higher in gastric cancer patients as compared to healthy controls. Moreover, it is closely correlated with various important clinic-pathological parameters such as tumor size, lymph node metastasis, tumor invasion depth, TNM stage, and survival rate.…”