title: Clinical and therapeutic relevance of PIM1 kinase in gastric cancer.
abstract: BACKGROUND
  Gastric cancer is a leading cause of cancer-related mortality, and chemotherapeutic options are currently limited. PIM1 kinase, an oncogene that promotes tumorigenesis in several cancer types, might represent a novel therapeutic target in gastric cancer.
  
  
  METHODS
  We studied the expression and genomic status of PIM1 in human primary gastric normal and tumor tissue samples by immunohistochemistry and array-based comparative genomic hybridization (aCGH). To ascertain whether PIM1 expression predicted susceptibility to PIM1 kinase-specific inhibition, the cytotoxic effect of a previously reported PIM1-specific small molecular inhibitor (K00135) was investigated in two gastric cancer cell lines with high (IM95) and undetectable (NUGC-4) PIM1 expression levels.
  
  
  RESULTS
  PIM1 expression was exclusively nuclear in normal gastric epithelial cells, while aberrant expression/localization (decreased nuclear and/or increased cytoplasmic expression) was observed in 75.6% (68/90) of the human gastric cancer tissue samples, with a significant inverse correlation between nuclear and cytoplasmic expression levels. Clinicopathological analyses revealed that decreased nuclear PIM1 expression correlated with poorer survival and greater depth of tumor invasion, while increased cytoplasmic PIM1 expression correlated inversely with the presence of lymphovascular invasion. High-level PIM1 amplification was identified in 10.5% of gastric cancers by aCGH. K00135 impaired the survival of IM95, while it had no significant effect on NUGC-4 survival.
  
  
  CONCLUSIONS
  Our findings demonstrate the clinical and therapeutic relevance of PIM1 in gastric cancers, and suggest that PIM1 represents a potential therapeutic target.
authors: Department of Pathology, National University Health System, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074, Singapore. tranceblues@gmail.com
authors: Benedict
authors: B
authors: Yan
authors: Ee Xuan
authors: EX
authors: Yau
authors: Sanjay
authors: S
authors: Samanta
authors: Chee Wee
authors: CW
authors: Ong
authors: Kol Jia
authors: KJ
authors: Yong
authors: Lai Kuan
authors: LK
authors: Ng
authors: Bhaskar
authors: B
authors: Bhattacharya
authors: Kiat Hon
authors: KH
authors: Lim
authors: Richie
authors: R
authors: Soong
authors: Khay Guan
authors: KG
authors: Yeoh
authors: Niantao
authors: N
authors: Deng
authors: Patrick
authors: P
authors: Tan
authors: Yulin
authors: Y
authors: Lam
authors: Manuel
authors: M
authors: Salto-Tellez
mesh_terms: D000368:Aged; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis; D051573:Proto-Oncogene Proteins c-pim-1 / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016019:Survival Analysis
chemical_list: C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1