title: Phosphorylated protein phosphatase 2A determines poor outcome in patients with metastatic colorectal cancer.
abstract: BACKGROUND
  Protein phosphatase 2A (PP2A) is a tumour suppressor frequently inactivated in human cancer and its tyrosine-307 phosphorylation has been reported as a molecular inhibitory mechanism.
  
  
  METHODS
  Expression of phosphorylated PP2A (p-PP2A) was evaluated in 250 metastatic colorectal cancer (CRC) patients. Chi-square, Kaplan-Meier and Cox analyses were used to determine correlations with clinical and molecular parameters and impact on clinical outcomes.
  
  
  RESULTS
  High p-PP2A levels were found in 17.2% cases and were associated with ECOG performance status (P=0.001) and presence of synchronous metastasis at diagnosis (P=0.035). This subgroup showed substantially worse overall survival (OS) (median OS, 6.0 vs 26.2 months, P<0.001) and progression-free survival (PFS) (median PFS, 3.8 vs 13.3 months, P<0.001). The prognostic impact of p-PP2A was particularly evident in patients aged <70 years (P<0.001). Multivariate analysis revealed that p-PP2A retained its prognostic impact for OS (hazard ratio 2.7; 95% confidence interval, 1.8-4.1; P<0.001) and PFS (hazard ratio 3.0; 95% confidence interval, 1.8-5.0; P<0.001).
  
  
  CONCLUSIONS
  Phosphorylated PP2A is an alteration that determines poor outcome in metastatic CRC and represents a novel potential therapeutic target in this disease, thus enabling to define a subgroup of patients who could benefit from future treatments based on PP2A activators.
authors.affiliation: Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz, UAM, University Hospital 'Fundacion Jimenez Diaz', E-28040 Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Cristóbal
authors.affiliation: Pathology Department, University Hospital 'Fundacion Jimenez Diaz', Autonomous University of Madrid, E-28040 Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Manso
authors.affiliation: Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz, UAM, University Hospital 'Fundacion Jimenez Diaz', E-28040 Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Rincón
authors.affiliation: Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz, UAM, University Hospital 'Fundacion Jimenez Diaz', E-28040 Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Caramés
authors.affiliation: Pathology Department, University Hospital 'Fundacion Jimenez Diaz', Autonomous University of Madrid, E-28040 Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Zazo
authors.affiliation: Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz, UAM, University Hospital 'Fundacion Jimenez Diaz', E-28040 Madrid, Spain.
authors.forename: T G
authors.initials: TG
authors.lastname: Del Pulgar
authors.affiliation: Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz, UAM, University Hospital 'Fundacion Jimenez Diaz', E-28040 Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Cebrián
authors.affiliation: Pathology Department, University Hospital 'Fundacion Jimenez Diaz', Autonomous University of Madrid, E-28040 Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Madoz-Gúrpide
authors.affiliation: Pathology Department, University Hospital 'Fundacion Jimenez Diaz', Autonomous University of Madrid, E-28040 Madrid, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Rojo
authors.affiliation: Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz, UAM, University Hospital 'Fundacion Jimenez Diaz', E-28040 Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: García-Foncillas
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000556:secondary; D008297:Male; D015999:Multivariate Analysis; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D016016:Proportional Hazards Models; D000071636:Protein Phosphatase 2C; D011499:Protein Processing, Post-Translational
chemical_list: D014408:Biomarkers, Tumor; D010750:Phosphoproteins; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C