Overexpression of B7H5/CD28H is associated with worse survival in human gastric cancer

Abstract

Gastric cancer (GC) is a common malignancy with low 5-year overall survival (OS). Recently, immune therapy has been used to treat cancer. B7H5 and CD28H are novel immune checkpoint molecules. However, the prognostic value of B7H5/CD28H expression in patients with GC remains unclear. In this study, seventy-one patients diagnosed with GC were included in this study. Patients' GC tissues and matched adjacent tissue constructed a tissue microarray. The expression levels of B7H5 and CD28H were examined using immunohistochemistry. Correlations between the expression of B7H5 and CD28H and the clinical data were evaluated. We found that the expression of B7H5 and CD28H (both P = .001) were higher in GC tumour tissues than in adjacent noncancerous tissues. B7H5/CD28H expression acted as an independent predictive factor in the OS of patients with GC. High expression of B7H5 and CD28H predicted poor outcome. Patients in the B7H5+CD28H+ group had a lower 5-year OS compared with patients in the B7H5-CD28- group (4.5% vs 55.6%, P = .001). A significant difference was found in the 5-year OS between patients in the B7H5+CD28H- and B7H5+CD28H+ groups (33.5% vs 4.5%, P = .006). However, there was no correlation between B7H5 and CD28H expression (P = .844). Therefore, B7H5 and CD28H expression are up-regulated in GC and are independent prognostic factors for overall survival in patients with GC. Although there was no correlation between B7H5 and CD28H expression, high expression of B7H5 and CD28H predicts poor prognosis, especially when both are highly expressed.

Keywords: B7 family checkpoints; B7H5; CD28H; gastric cancer; immunotherapy.

Figure 1

Expression of B7H5 in gastric carcinoma and noncancerous tissues. A‐C, High/middle/low expression of B7H5 in gastric carcinoma. D‐F, High/middle/low expression of B7H5 in noncancerous tissues

Figure 2

B7H5 protein was expressed in both gastric carcinoma and noncancerous tissues. A, B7H5 expression was higher in cytoplasm in GC tissues than in gastric tissue (P = .001); B, B7H5 expression was higher in the nucleus in GC tissues than in gastric tissue (P < .001); C, CD28h expression was higher in immune cells in GC tissues than in gastric tissue (P = .001); D, There was no correlation between B7H5 and CD28H expression (P = .844)

Figure 3

Expression of CD28H in gastric carcinoma and noncancerous tissues. A‐C, High/middle/low expression of CD28H in gastric carcinoma. D‐F, High/middle/low expression of CD28H in noncancerous tissues

Figure 4

CD28H is expression on T cells in GC tissues and gastric tissues. A‐B, Representative flow cytometry plots showing the count of CD3⁺T cells in GC tissues and gastric tissues. C, The mean percentages showed that the count of CD3⁺T cells in GC tissues was higher than that than gastric tissues, *, P < .05. D‐E, Representative flow cytometry plots showing the count of CD3⁺CD28H⁺T cells in CD3⁺ T cells in GC tissues and gastric tissues. F, The mean percentages showed that the count of CD3⁺ CD28H⁺T cells in CD3⁺ T cells in GC tissues was higher than that in gastric tissues, *, P < .05

Figure 5

Correlation of B7H5/CD28H expression level and overall survival (OS) in GC patients. A, There is no difference in 5‐year OS between high B7H5 expression and low expression in the nuclei in patients with GC (28.0% vs 21.6%, P = .254); B, High B7H5 expression predicted poorer survival than low B7H5 expression in patients with GC (19.6% vs 37.5%, P = .035); C, High CD28H expression predicted poorer survival than low CD28H expression in patients with GC (39.4% vs 6.9%, P = .002); D, Patients in the B7H5⁺CD28H⁺ group have a lower 5‐year OS compared with patients in the B7H5⁻CD28⁻ group (4.5% vs 55.6%, P = .001), a significant difference was found in the 5‐year OS between patients in B7H5⁺CD28H⁻ and B7H5⁺CD28H⁺ groups (33.5% vs 4.5%, P = .006), and there was no significant difference between the B7H5⁻CD28⁻ group and the B7H5⁻CD28H⁺ group (55.6% vs 33.3%, P = .111)