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

Abstract

BackgroundGastric 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. MethodsWe 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. ResultsThere was a significant correlation between B7-H3 and HER2 expression in GC tissues. High co-expression 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. ConclusionHigh 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.