title: [Correlation between Gli1 expression and clinicopathological significance in human pancreatic cancer].
abstract: OBJECTIVE
  To study the clinicopathological significance and relationship of Gli1, MDM2 and p53 expression in human pancreatic cancer.
  
  
  METHODS
  The expression of Gli1, MDM2 and p53 proteins in 57 paired paraffin embedded pancreatic ductal adenocarcinoma (PDAC) specimens and adjacent non-cancerous pancreatic tissues was detected by immunohistochemistry. The relationship between their expression and clinicopathological characters was analyzed. Quantitative real-time PCR (qRT-PCR) was used to examine the expression of Gli1 mRNA level in 14 paired fresh PDAC specimens and adjacent non-cancerous pancreatic tissues. siRNA interference were used to further detect the close relationship among them.
  
  
  RESULTS
  IHC showed the expression of Gli1 (50.9%), MDM2 (57.9%) and p53 (56.1%) was increased in 57 cases of pancreatic cancer compared to that in paired normal pancreatic tissues (33.3%, 26.3% and 17.5% respectively, t = 2.413, 2.848 and 2.960, all P < 0.05). Gli1 expression was positively associated with tumor TNM stage (χ(2) = 8.211, P = 0.004), invasion depth (χ(2) = 4.247, P = 0.039) and MDM2 expression (r = 0.299, χ(2) = 5.105, P = 0.024), while expression of MDM2 and p53 was associated with tumor invasion depth (χ(2) = 5.182, P = 0.023) and TNM stage (χ(2) = 5.696, P = 0.017), respectively. Univariate and multivariate analysis revealed that Gli1 was an independent adverse prognostic indicator for patients with PDAC (RR = 2.290, 95%CI: 1.051-4.992, P = 0.037), and patients with Gli1 and MDM2 co-expression had a significantly poorer overall survival than patients with their negative expression (P = 0.034). Gli1 mRNA expression was much higher in 14 cases of PDAC than that in adjacent normal pancreatic tissues (t = 2.926, P = 0.012). In p53 mutant AsPC-1 cells, Gli1 knockdown down regulated MDM2, but had no effect on p53 expression, whereas Gli1 knockdown down regulated MDM2 and up regulated p53 protein levels in p53 wild-type Capan-2 cells.
  
  
  CONCLUSIONS
  Gli1, MDM2 and p53 are overexpressed in PDAC, and are benefit for predicting patients' prognosis. Gli1can regulate MDM2 and wild-type p53 expression. Their co-expression might coordinately contribute to the development and progression of PDAC.
authors.affiliation: Department of Gastrointestinal Surgery, the First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Wei-wei
authors.initials: WW
authors.lastname: Sheng
authors.forename: Ming
authors.initials: M
authors.lastname: Dong
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Zhou
authors.forename: Qing-feng
authors.initials: QF
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Email: cmudongming@sohu.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Dong
mesh_terms: D000328:Adult; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
chemical_list: D015513:Oncogene Proteins; D012333:RNA, Messenger; C495901:TP53 protein, human; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D000071676:Zinc Finger Protein GLI1; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2