title: The expression of both peroxisome proliferator-activated receptor delta and cyclooxygenase-2 in tissues is associated with poor prognosis in colorectal cancer patients.
abstract: BACKGROUND
  The role of peroxisome proliferator-activated receptor delta (PPAR δ) in the development and progression of colorectal cancer (CRC) remains controversial.
  
  
  OBJECTIVE
  We investigated the impact of PPAR δ expression in tissues on liver metastasis of CRC.
  
  
  METHODS
  We analyzed samples of primary CRC and matched normal adjacent tissues from 52 patients for the expression of PPAR δ, cyclooxygenase (COX)-2, vascular endothelial growth factor (VEGF)-A, and CXC chemokine receptor 4 (CXCR4). Correlations of the molecules expressions with clinical characteristics and prognosis of patients were studied.
  
  
  RESULTS
  The number of patients positive for PPAR δ, COX-2, CXCR4, and VEGF-A was 25, 33, 18, and 19, respectively. Among the PPAR δ (+)/COX-2 (+), PPAR δ (-)/COX-2 (+), PPAR δ (+)/COX-2 (-), and PPAR δ (-)/COX-2 (-) patient groups, PPAR δ (+)/COX-2 (+) patients had the highest incidence of liver metastasis (p<0.01). PPAR δ (+)/COX-2 (+) expression was a significant independent prognostic factor (HR=7.108, 95% CI 1.231-41.029, p=0.0283) by Cox proportional analysis. PPAR δ (+)/COX-2 (+) patients had the highest positivity for CXCR4 or VEGF-A in tissues (p<0.01). Among the patients in the CXCR4 (+)/VEGF-A (+), CXCR4 (+)/VEGF-A (-), CXCR4 (-)/VEGF-A (+), and CXCR4 (-)/VEGF-A (-) groups, CXCR4 (+)/VEGF-A (+) patients had the highest incidence of liver metastasis (p<0.01).
  
  
  CONCLUSIONS
  The expression of both PPAR δ and COX-2 in tissues may lead to liver metastasis and consequent poor prognosis in CRC patients.
authors.affiliation: Department of Gastroenterology, Hepatology, and Nutrition, National Hospital Organization Beppu Medical Center, 1473 Uchikamado, Beppu, Oita, 874-0011, Japan. masahiro@beppu.hosp.go.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yoshinaga
authors.forename: Kentaro
authors.initials: K
authors.lastname: Taki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Somada
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Sakiyama
authors.forename: Norihiko
authors.initials: N
authors.lastname: Kubo
authors.forename: Toyoma
authors.initials: T
authors.lastname: Kaku
authors.forename: Satoru
authors.initials: S
authors.lastname: Tsuruta
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kusumoto
authors.forename: Hironori
authors.initials: H
authors.lastname: Sakai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Muto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000378:metabolism / Q000556:secondary*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D047494:PPAR delta / Q000096:biosynthesis*; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: C527276:CXCR4 protein, human; D047494:PPAR delta; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2
references.citation: Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2598-603
references.pmid: 11226285
references.citation: Oncogene. 2006 Feb 23;25(8):1225-41
references.pmid: 16288226
references.citation: J Invest Surg. 2009 Mar-Apr;22(2):105-11
references.pmid: 19283612
references.citation: Cell Cycle. 2004 Dec;3(12):1512-5
references.pmid: 15539957
references.citation: Cancer Cell. 2004 Sep;6(3):285-95
references.pmid: 15380519
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12890-5
references.pmid: 17652168
references.citation: J Natl Cancer Inst. 2009 May 20;101(10):762-7
references.pmid: 19436036
references.citation: Clin Cancer Res. 2000 Jul;6(7):2803-7
references.pmid: 10914727
references.citation: Cell. 1999 Oct 29;99(3):335-45
references.pmid: 10555149
references.citation: Semin Surg Oncol. 1993 May-Jun;9(3):256-63
references.pmid: 8516614
references.citation: Clin Cancer Res. 2006 May 1;12(9):2795-803
references.pmid: 16675573
references.citation: Oncol Rep. 2007 Mar;17(3):525-30
references.pmid: 17273728
references.citation: Jpn J Clin Oncol. 2007 Sep;37(9):679-85
references.pmid: 17846040
references.citation: Nat Med. 2004 May;10(5):481-3
references.pmid: 15048110
references.citation: Nat Med. 2004 Mar;10(3):245-7
references.pmid: 14758356
references.citation: Breast Cancer Res. 2003;5(5):R144-50
references.pmid: 12927045
references.citation: Int J Oncol. 2007 May;30(5):1215-22
references.pmid: 17390024
references.citation: Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13275-80
references.pmid: 11087869
references.citation: Blood. 2006 Mar 1;107(5):1761-7
references.pmid: 16269611
references.citation: Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7355-9
references.pmid: 8041794
references.citation: Methods Mol Biol. 2009;512:295-307
references.pmid: 19347284
references.citation: Exp Cell Res. 2003 Nov 1;290(2):289-302
references.pmid: 14567988
references.citation: Exp Cell Res. 2007 Oct 1;313(16):3446-58
references.pmid: 17707368
references.citation: Oncogene. 2004 Nov 25;23(55):8992-6
references.pmid: 15480419
references.citation: Br J Cancer. 2006 Oct 9;95(7):889-95
references.pmid: 16969348
references.citation: Nat Rev Cancer. 2002 Aug;2(8):563-72
references.pmid: 12154349
references.citation: Cancer Res. 2003 Apr 15;63(8):1748-51
references.pmid: 12702555
references.citation: Clin Cancer Res. 2005 Mar 1;11(5):1743-50
references.pmid: 15755995
references.citation: Neoplasia. 2009 Jul;11(7):651-61
references.pmid: 19568410