Trancriptome sequencing of BGC823 with or without ZBTB7A knockdown

Tumor budding (TB), clusters of less than 5 cells dissociated from the tumor mass, is reported to predict nodal involvement and recurrence in multiple human cancers including gastric carcinoma (GC). However, it is not clear how TB forms. In this study, we determined the expression pattern of GAGE12I, CTNND1, Kif26B, CREB1 and ZBTB7A in human GC samples by IHC attempting to find any TB-related markers. The results showed that TB could predict lymph node metastasis and is negatively associated with the overall survival of GC patients. The expression of ZBTB7A in the tumor margin (invasive front), rather than the other four markers, was much higher than that inside the tumor and was positively correlated with TB score. Moreover, patients with higher marginal ZBTB7A expression had poorer prognosis. ZBTB7A could enhance the migration and invasion capabilities of GC cells in vitro. Mechanically, ZBTB7A might activate EGFR-MAPK-ERK and PI3K-AKT-mTOR pathway, which resulted in epithelial-mesenchymal transition (EMT) to induce the formation of TB. Thus, we concluded that higher ZBTB7A expression in the tumor margin may contribute to the dissociation of tumor cells from the tumor mass to form TB by initiating EMT via EGFR-MEK-ERK and PI3K-AKT-mTOR pathway. Overall design: BCG823 cells of control and that with siZBTB7A treated were analyzed. No replication.