title: Increased CDC20 expression is associated with pancreatic ductal adenocarcinoma differentiation and progression.
abstract: OBJECTIVE
  Cell division cycle 20 (CDC20) homolog is an anaphase-promoting complex activator that is essential for cell division, but whether its expression in pancreatic ductal adenocarcinoma (PDAC) is significant is unknown. In this retrospective study, we determined whether aberrant CDC20 expression can be used as a biomarker in pancreatic ductal adenocarcinoma (PDAC) tumorigenesis and whether its expression reflects clinical progression.
  
  
  METHODS
  We compared CDC20 expression levels in normal, cancerous, and inflamed pancreatic tissues from stage II PDAC patients with clinical outcomes and determined CDC20 levels in seven PDAC cell lines. CDC20 was identified using a cDNA microarray database containing gene expression profiles for PDAC tissues and cell lines and chronic pancreatitis and normal pancreas tissues. Its expression was confirmed by real-time quantitative reverse-transcriptase-polymerase chain reaction (qRT-PCR). An immunohistochemical analysis of tissue microarrays from resected PDAC tumors and paired benign pancreatic tissues was done and CDC20 levels were correlated with clinical outcome.
  
  
  RESULTS
  Fifty-six patients were included in this study. A microarray analysis revealed 5-fold higher CDC20 expression in PDAC tissue than in chronic pancreatitis tissue. A qRT-PCR analysis confirmed a mean 20-fold higher CDC20 level in PDAC tissue than in normal pancreas and pancreatitis tissue. RNA and protein CDC20 expression was detected in several PDAC cell lines. An immunohistochemical analysis revealed higher CDC20 protein expression levels in PDAC tissue than in normal pancreas tissue, and high CDC20 expression was associated with poor differentiation (P = 0.020) and a significantly lower 5-year recurrence-free survival rate (P = 0.039); we also found a trend toward a shorter overall survival duration.
  
  
  CONCLUSIONS
  Aberrant CDC20 expression may play an important role in PDAC tumorigenesis and progression and may thus be useful as a marker of disease progression and prognosis and as a therapeutic target.
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. David.Chang@USOncology.com
authors.forename: David Z
authors.initials: DZ
authors.lastname: Chang
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.forename: Baoan
authors.initials: B
authors.lastname: Ji
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: Craig
authors.initials: C
authors.lastname: Logsdon
authors.forename: Huamin
authors.initials: H
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D015854:Up-Regulation / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; C577488:CDC20 protein, human