High expression of Annexin A2 is associated with DNA repair, metabolic alteration, and worse survival in pancreatic ductal adenocarcinoma.

Abstract

Annexin A2 (ANXA2) is a known driver of cancer progression. We investigated what mechanism associates with ANXA2 high expression and its survival impact using a bioinformatic approach in pancreatic ductal adenocarcinoma. Primary pancreatic tumor (n = 185) cohort in The Cancer Genome Atlas and Gene set enrichment analysis were used. There were no significant associations between ANXA2 expression and clinicopathologic features of the patients investigated. The ANXA2 high tumors enriched some of the known downstream signaling, such as NF-κB (P = .028) and tumor necrosis factor (P = .044) pathways, whereas others, such as angiogenesis or epithelial-mesenchymal transition, were not associated. ANXA2 high expression tumors enriched DNA repair-related gene sets (DNA repair; P = .011, p53 pathway; P = .036) and cell proliferation-related gene sets (MYC targets; P = .041). In addition, new association with metabolism related gene sets, such as glycolysis (P = .016), nucleic acid metabolism (P = .001), and pyrimidine metabolism (P = .004) were identified in the ANXA2 high group. Patients with high ANXA2 expression demonstrated significantly worse disease-free survival (P = .001) and overall survival (P = .014), with high ANXA2 being an independent risk factor. High ANXA2 expression was associated with NF-κB and tumor necrosis factor signaling, DNA repair, cell proliferation, and metabolic alteration and worse prognosis in pancreatic ductal adenocarcinoma.