title: Annexin A8 Is a Prognostic Marker and Potential Therapeutic Target for Pancreatic Cancer.
abstract: OBJECTIVE
  We investigated whether annexin A8 (A-A8), a Ca-binding protein overexpressed in pancreatic cancer, plays a role in cell growth and migration and investigated its association with pancreatic cancer prognosis.
  
  
  METHODS
  Clinicopathological features and associations between increased A-A8 expression (determined by immunohistochemistry) and histologic grade were studied in a tissue microarray of 90 patients with resected stage I/II pancreatic cancer. We investigated A-A8's effect on cell migration, proliferation, and colony formation in 2 pancreatic cancer cells (BXPC-3 and Panc-1). Statistical analyses included Fisher exact test, t test, analysis of variance, and survival analysis.
  
  
  RESULTS
  Western blot showed increased A-A8 expression in human pancreatic cancer cells, with A-A8 knockdown in BXPC-3 and Panc-1 cells demonstrating decreased cell viability (P = 0.017 and P = 0.001), migration (2.5 vs 0.9 mm and 1.6 vs 1 mm at 96 hours; P = 0.048 and P = 0.004), and colony formation (approximately 75% and 40% from scramble; P ≤ 0.01), respectively. In our tissue microarray, A-A8 expression increased 5.9-fold (r = 0.31; P = 0.019) from low- to high-grade tumors, correlating with tumor grade (r = 0.23; P = 0.027). In addition, high A-A8 expression was associated with a decreased 5-year survival (P = 0.042).
  
  
  CONCLUSIONS
  Our study is the first showing that increased A-A8 expression is associated with poor prognosis in early-stage pancreatic cancer, thus supporting its further investigation as a future therapeutic target and prognostic marker.
authors.affiliation: From the Departments of *Gastrointestinal Oncology, †Epidemiology, and ‡Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute; and §Morsani Medical School, University of South Florida, Tampa, FL.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Pimiento
authors.forename: Dung-Tsa
authors.initials: DT
authors.lastname: Chen
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Centeno
authors.forename: Ashley H
authors.initials: AH
authors.lastname: Davis-Yadley
authors.forename: Kazim
authors.initials: K
authors.lastname: Husain
authors.forename: William J
authors.initials: WJ
authors.lastname: Fulp
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Anying
authors.initials: A
authors.lastname: Zhang
authors.forename: Mokenge P
authors.initials: MP
authors.lastname: Malafa
mesh_terms: D017302:Annexins / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018572:Disease-Free Survival; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011446:Prospective Studies; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D046888:Tissue Array Analysis; D014162:Transfection; D015854:Up-Regulation
chemical_list: D017302:Annexins; D014408:Biomarkers, Tumor