title: Biological function and prognostic significance of peroxisome proliferator-activated receptor δ in rectal cancer.
abstract: OBJECTIVE
  To investigate the expression significance of PPAR β/δ in relation to radiotherapy (RT), clinicopathologic, and prognostic variables of rectal cancer patients.
  
  
  METHODS
  We included 141 primary rectal cancer patients who participated in a Swedish clinical trial of preoperative RT. Tissue microarray samples from the excised rectal cancers and the adjacent or distant normal mucosa and lymph node metastases were stained with PPAR δ antibody. Survival probability was computed by the Kaplan-Meier method and Cox regression model. The proliferation of colon cancer cell lines KM12C, KM12SM, and KM12L4a was assayed after PPAR δ knockdown.
  
  
  RESULTS
  PPAR δ was increased from adjacent or distant normal mucosa to primary cancers, whereas it decreased from primary cancers to lymph node metastases. After RT, PPAR δ was increased in normal mucosa, whereas it decreased in primary cancers and lymph node metastases. In primary cancers, the high expression of PPAR δ was related to higher frequency of stage I cases, lower lymph node metastasis rate, and low expression of Ki-67 in the unirradiated cases, and related to favorable survival in the cases either with or without RT. The proliferation of the KM12C, KM12SM, or KM12L4a cells was significantly accelerated after PPAR δ knockdown.
  
  
  CONCLUSIONS
  RT decreases the PPAR δ expression in primary rectal cancers and lymph node metastases. PPAR δ is related to the early development of rectal cancer and inhibits the proliferation of colorectal cancer cells. Increase of PPAR δ predicts favorable survival in the rectal cancer patients either with or without preoperative RT.
authors.affiliation: Institute of Digestive Surgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors.forename: Lie
authors.initials: L
authors.lastname: Yang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Zong-Guang
authors.initials: ZG
authors.lastname: Zhou
authors.forename: Hui
authors.initials: H
authors.lastname: Yan
authors.forename: G
authors.initials: G
authors.lastname: Adell
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Sun
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000235:genetics; D008207:Lymphatic Metastasis; D008297:Male; D009092:Mucous Membrane / Q000166:cytology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D047494:PPAR delta / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D011379:Prognosis; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis; D012004:Rectal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000532:radiotherapy; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D047494:PPAR delta; D000077022:Survivin; D051546:Cyclooxygenase 2; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases