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

Surgery. 2019 Aug;166(2):150-156. doi: 10.1016/j.surg.2019.04.011. Epub 2019 Jun 3.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Annexin A2 / genetics*
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / mortality*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cohort Studies
  • DNA Repair / genetics
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / mortality*
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Registries
  • Retrospective Studies
  • Signal Transduction / genetics
  • Survival Analysis

Substances

  • Annexin A2
  • NF-kappa B