Clinical significance of B7-H3 and HER2 co-expression and therapeutic value of combination treatment in gastric cancer

Background: Gastric cancer (GC) is a digestive system malignancy. Trastuzumab (a HER2-targeted monoclonal antibody) is an important targeted drug for GC. However, the drug resistance limits its clinical efficacy. B7-H3 was suggested to be a promising target for cancer immunotherapy. This study aimed to investigate the clinical significance of B7-H3 and HER2 co-expression and the therapeutic value of combination treatment in GC.Methods: We examined the expression of B7-H3 and HER2 in 268 GC patients by immunohistochemistry. Pearson test was used to analyze the correlation between categorical variables. Overall survival was assessed by Kaplan-Meier analysis. All in vitro experiments using HER2-positive GC cells were treated with small interfering RNA targeting B7-H3/HER2 or B7-H3 blocking antibody 3E8/trastuzumab to verify the antitumor efficacy of the combination therapy. GC xenograft mouse models were established to evaluate the in vivo anti-tumor effect of combined therapy.Results: There was a significant correlation between B7-H3 and HER2 expression in GC tissues. High coexpression of B7-H3 and HER2 was associated with poor prognosis (P = 0.007) and could be an independent risk factor for survival. In addition, knockdown or targeted therapies of B7-H3/HER2 significantly suppressed cell proliferation, migration, invasion and adhesion in vitro. Trastuzumab combined with 3E8 was significantly effective at reducing mice tumor growth than monotherapy.Conclusion: High co-expression of B7-H3 and HER2 indicates a poor prognosis, and combination therapy targeting B7-H3 and HER2 could be an immunotherapeutic strategy for GC.