title: Pituitary tumor-transforming gene-1 serves as an independent prognostic biomarker for gastric cancer.
abstract: BACKGROUND
  Pituitary tumor-transforming gene-1 (PTTG1) is a transcription factor that can affect transcriptional activity, angiogenesis, and cell senescence. We examined PTTG1 mRNA and protein expression in gastric cancer (GC) cell lines and tissues to determine its value as a biomarker for GC diagnosis and therapy.
  
  
  METHODS
  PTTG1 mRNA expression from 78 GC cases and paired adjacent normal mucosa (PCR cohort) as well as from five gastric cell lines was assessed using qRT-PCR. Nuclear and cytoplasmic RNA were extracted from two gastric cell lines to determine PTTG1 mRNA localization. PTTG1 protein expression from 98 GC cases, their paired adjacent normal mucosa, and 23 gastric intraepithelial neoplasia (GIN) cases was examined using immunohistochemistry (IHC cohort). The correlation between PTTG1 mRNA and protein expression and GC clinicopathological parameters was analyzed.
  
  
  RESULTS
  PTTG1 mRNA expression in GC tissues and cell lines was significantly increased compared with adjacent normal gastric mucosa and normal gastric mucous cell lines (p < 0.05). PTTG1 expression was nuclear and cytoplasmic, with higher cytoplasmic expression. PTTG1 immunostaining significantly differed in GC (95.66 ± 20.65), GIN (84.00 ± 34.16), and normal adjacent mucosa (28 ± 22.25) (p < 0.001). Multivariate Cox regression analysis revealed that PTTG1 mRNA and protein expression are independent prognostic factors for GC patient survival.
  
  
  CONCLUSIONS
  Our results suggest that PTTG1 is a promising target for GC diagnosis and therapy.
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. xumd27202003@sina.com.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. xumd27202003@sina.com.|Institute of Pathology, Fudan University, Shanghai, 200032, China. xumd27202003@sina.com.
authors: Mi-die
authors: MD
authors: Xu
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Institute of Pathology, Fudan University, Shanghai, 200032, China.
authors: Lei
authors: L
authors: Dong
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Institute of Pathology, Fudan University, Shanghai, 200032, China.
authors: Peng
authors: P
authors: Qi
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Institute of Pathology, Fudan University, Shanghai, 200032, China.
authors: Wei-wei
authors: WW
authors: Weng
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Institute of Pathology, Fudan University, Shanghai, 200032, China.
authors: Xiao-han
authors: XH
authors: Shen
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Institute of Pathology, Fudan University, Shanghai, 200032, China.
authors: Shu-juan
authors: SJ
authors: Ni
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Institute of Pathology, Fudan University, Shanghai, 200032, China.
authors: Dan
authors: D
authors: Huang
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Institute of Pathology, Fudan University, Shanghai, 200032, China.
authors: Cong
authors: C
authors: Tan
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Institute of Pathology, Fudan University, Shanghai, 200032, China.
authors: Wei-qi
authors: WQ
authors: Sheng
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Institute of Pathology, Fudan University, Shanghai, 200032, China.
authors: Xiao-yan
authors: XY
authors: Zhou
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. dx2008cn@163.com.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. dx2008cn@163.com.|Institute of Pathology, Fudan University, Shanghai, 200032, China. dx2008cn@163.com.|Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China. dx2008cn@163.com.
authors: Xiang
authors: X
authors: Du
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D064249:Securin / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human
keywords: Gastric cancer; Immunohistochemistry; PTTG1; Prognosis
references: Endocr Relat Cancer. 2008 Sep;15(3):721-43
references: 18753362
references: Cancer Res. 2012 Sep 1;72(17):4361-71
references: 22805307
references: J Mol Endocrinol. 2009 Feb;42(2):87-103
references: 18984771
references: J Carcinog. 2006 Jan 20;5:4
references: 16426442
references: J Biol Chem. 2000 Oct 6;275(40):31191-8
references: 10906323
references: Carcinogenesis. 2007 Mar;28(3):749-59
references: 17071631
references: J Mol Endocrinol. 2009 Nov;43(5):179-85
references: 19433493
references: Surgery. 2013 Dec;154(6):1405-16; discussion 1416
references: 24238056
references: Pathology. 2001 Feb;33(1):21-5
references: 11280603
references: J Transl Med. 2013 May 16;11:122
references: 23680400
references: Lancet. 2000 Feb 26;355(9205):716-9
references: 10703804
references: Science. 1999 Jul 16;285(5426):418-22
references: 10411507
references: Acta Pathol Microbiol Scand. 1965;64:31-49
references: 14320675
references: Andrologia. 2015 May;47(4):427-32
references: 24754453
references: Mol Med Rep. 2013 Jan;7(1):43-6
references: 23128677
references: Breast. 2004 Feb;13(1):80-1
references: 14759723
references: Ann Oncol. 2007 Jun;18 Suppl 6:vi120-3
references: 17591804
references: J Clin Oncol. 2006 May 10;24(14):2137-50
references: 16682732
references: Am J Gastroenterol. 2001 Apr;96(4):1313-4
references: 11316206
references: Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):1008-13
references: 24395789
references: Cytokine Growth Factor Rev. 2006 Jun;17(3):147-56
references: 16516532
references: J Clin Endocrinol Metab. 1999 Feb;84(2):761-7
references: 10022450
references: J Biol Chem. 2000 Jun 23;275(25):19422-7
references: 10781616
references: J Surg Res. 2005 Nov;129(1):142-6
references: 15936773
references: Mol Cancer. 2006 Nov 10;5:61
references: 17096843
references: Mol Endocrinol. 1997 Apr;11(4):433-41
references: 9092795
references: World J Gastroenterol. 2004 Feb 15;10(4):481-3
references: 14966902
references: J Ovarian Res. 2008 Oct 20;1(1):6
references: 19014669
references: Cancer Res. 2009 Apr 15;69(8):3283-90
references: 19351864