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

Background: 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. Methods: Primary pancreatic tumor (n = 185) cohort in The Cancer Genome Atlas and Gene set enrichment analysis were used. Results: 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. Conclusion: 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.