title: The opposite prognostic significance of nuclear and cytoplasmic p21 expression in resectable gastric cancer patients.
abstract: BACKGROUND
  Protein p21(Cip1/Waf1) is a cyclin-dependent kinase inhibitor, which plays important roles in cell cycle arrest, senescence, and apoptosis. Interestingly, the nuclear and cytoplasmic p21 executes various functions in the cell. In this study, we investigated the prognostic impact of subcellular p21 expression in gastric cancer (GC).
  
  
  METHODS
  Expressions of subcellular p21 was assessed by immunohistochemistry using a tissue microarray in a training cohort and it went into a second testing cohort and finally to a validating cohort. Prognostic and predictive role of subcellular p21 expression status was evaluated. We also studied the roles of subcellular p21 in GC cell migration and invasion.
  
  
  RESULTS
  Nuclear and cytoplasmic p21 protein levels were significantly reduced and increased in GC lesions compared with adjacent non-cancerous tissues, respectively. Low nuclear p21 or high cytoplasmic p21 expression significantly correlated with shorter overall survival (OS), as well as with clinicopathologic characteristics in patients. Multivariate regression analysis showed that low nuclear and high cytoplasmic p21 expression, separately and together, were independent negative markers of OS. Finally, we found that nuclear p21 inhibits but cytoplasmic p21 promotes cell migration and invasion abilities.
  
  
  CONCLUSIONS
  These findings suggest that nuclear and cytoplasmic p21 protein expression in tumor are novel candidate prognostic markers in resectable human gastric carcinoma, and they exert distinct roles in cell migration and invasion.
authors.affiliation: Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, People's Republic of China.
authors.forename: Yefei
authors.initials: Y
authors.lastname: Huang
authors.forename: Weimin
authors.initials: W
authors.lastname: Wang
authors.forename: Yansu
authors.initials: Y
authors.lastname: Chen
authors.forename: Yulin
authors.initials: Y
authors.lastname: Huang
authors.forename: Jianbing
authors.initials: J
authors.lastname: Zhang
authors.forename: Song
authors.initials: S
authors.lastname: He
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Tan
authors.forename: Fulin
authors.initials: F
authors.lastname: Qiang
authors.forename: Aiping
authors.initials: A
authors.lastname: Li
authors.forename: Oluf Dimitri
authors.initials: OD
authors.lastname: Røe
authors.forename: Shouyu
authors.initials: S
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D013347:Subcellular Fractions; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21