title: Differential expression of cytochrome P450 omega-hydroxylase isoforms and their association with clinicopathological features in pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  The cytochrome P450 (CYP) superfamily consists of enzymes that catalyze the oxidation of lipids, steroids, and drugs. In particular, the CYP4 family plays an essential role in lipid metabolism by the ω-hydroxylation of terminal ends of fatty acids. Disturbance of this system has been associated with increased angiogenesis, proliferation, and metastasis of several cancers. This study aimed to detect the expression of CYP4 isoforms (CYP4A11, CYP4F2, CYP4F3) in pancreatic ductal adenocarcinoma (PDA) and their association with clinicopathological features.
  
  
  METHODS
  Pancreatic specimens were collected from 73 patients who underwent surgical resection at the Thomas Jefferson University Hospital. Quantitative polymerase chain reaction was used to examine the cytochrome P450 isoforms in PDA (n = 62), adjacent-normal (n = 30), and benign tissues (n = 11). Logistic regression models were used to analyze gene expression among tissue types. Spearman rank correlations were calculated for isoform expression and for age. Differences in expression by gender were assessed via t test. Other clinicopathological variables (diabetes, smoking, obesity, T stage, perineural invasion, nodal status) were analyzed by Wilcoxon rank sum.
  
  
  RESULTS
  CYP4 expression for isoforms was significantly higher in PDA tissues versus matched-adjacent tissues (p < 0.01). PDA tumors expressed significantly higher levels of CYP4F2 and CYP4F3 when compared to benign lesions (p < 0.01). Significant associations were found between low levels of CYP4F2 and CYP4F3 and increased age of PDA patients. Interestingly, all isoforms were expressed at higher levels in male patients.
  
  
  CONCLUSIONS
  Transcriptional upregulation of cytochrome P450 ω-hydroxylase suggests that these enzymes have the potential to be used as distinguishing markers in pancreatic pathology.
authors.affiliation: Department of Surgery, Jefferson Pancreatic Biliary and Related Cancer Center, Thomas Jefferson University Hospital, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Ankit V
authors.initials: AV
authors.lastname: Gandhi
authors.forename: Shivam
authors.initials: S
authors.lastname: Saxena
authors.forename: Daniel
authors.initials: D
authors.lastname: Relles
authors.forename: Konrad
authors.initials: K
authors.lastname: Sarosiek
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Kang
authors.forename: Galina
authors.initials: G
authors.lastname: Chipitsyna
authors.forename: Jocelyn Andrel
authors.initials: JA
authors.lastname: Sendecki
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Yeo
authors.forename: Hwyda A
authors.initials: HA
authors.lastname: Arafat
mesh_terms: D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007527:Isoenzymes; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010179:Pancreas / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; C409986:cytochrome P-450 omega-hydroxylase