TNFR2 mediates pancreatic cancer proliferation, migration, and invasion via the NF‑κB signaling pathway

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant disease with low overall survival; chemotherapy and immunotherapy have limited efficacy. Tumor necrosis factor receptor 2 (TNFR2) contributes to the development and progression of several tumors. In this study, we investigated the clinicopathologic data and outcomes of pancreatic cancer patients and elucidated the molecular mechanisms of TNFR2. Method: We used The Cancer Genome Atlas and the Genotype-Tissue Expression database to compare the expression of the TNFR2 gene between normal (n = 171) and malignant (n = 179) pancreatic tissue. Using immunohistochemical staining, we divided the patients into high and low-expression groups, then investigated clinicopathologic data and survival curves of pancreatic cancer patients. We measured TNFR2 protein expression in PANC-1 and ASPC-1 pancreatic cancer cells subjected to TNFR2 small interfering RNA or negative control treatment. We performed proliferation, invasion, and migration assays to study the biological effects of TNFR2 in PDAC. The molecular mechanisms were validated using western blotting. Results: TNFR2 was more highly expressed in PDAC cells and tissues than in controls. Abundant expression of TNFR2 was associated with aggressive clinicopathologic characteristics and poor outcomes. Overexpression of TNFR2 promoted PDAC cell proliferation, migration, and invasion in vitro. Mechanistically, TNFR2 binds to TNF-ɑ and activates the NF-κB signaling pathway. Conclusion: TNFR2 is a prognostic marker that facilitates the proliferation, migration, and invasion of PDAC via the NF‑κB signaling pathway. TNFR2 may become a therapeutic target.