Hideo Takahashi1, Eriko Katsuta1, Li Yan2, Subhamoy Dasgupta3, Kazuaki Takabe4. 1. Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY. 2. Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY. 3. Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY. 4. Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY; Department of Surgery, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, the State University of New York, Buffalo, NY; Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo, Japan; Department of Surgery, Yokohama City University, Yokohama, Japan; Department of Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. Electronic address: kazuaki.takabe@roswellpark.org.
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.
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.
Authors: I Keklikoglou; K Hosaka; C Bender; A Bott; C Koerner; D Mitra; R Will; A Woerner; E Muenstermann; H Wilhelm; Y Cao; S Wiemann Journal: Oncogene Date: 2014-12-15 Impact factor: 9.867
Authors: Cosimo Commisso; Shawn M Davidson; Rengin G Soydaner-Azeloglu; Seth J Parker; Jurre J Kamphorst; Sean Hackett; Elda Grabocka; Michel Nofal; Jeffrey A Drebin; Craig B Thompson; Joshua D Rabinowitz; Christian M Metallo; Matthew G Vander Heiden; Dafna Bar-Sagi Journal: Nature Date: 2013-05-12 Impact factor: 49.962