title: Protein phosphatase methylesterase-1 (PME-1) expression predicts a favorable clinical outcome in colorectal cancer.
abstract: Colorectal cancer (CRC) accounts for high mortality. So far, there is lack of markers capable of predicting which patients are at risk of aggressive course of the disease. Protein phosphatase-2A (PP2A) inhibitor proteins have recently gained interest as markers of more aggressive disease in certain cancers. Here, we report the role of PP2A inhibitor PME-1 in CRC. PME-1 expression was assessed from a rectal cancer patient cohort by immunohistochemistry, and correlations were performed for various clinicopathological variables and patient survival. Rectal cancer patients with higher cytoplasmic PME-1 protein expression (above median) had less recurrences (P = 0.003, n = 195) and better disease-free survival (DFS) than the patients with low cytoplasmic PME-1 protein expression (below median). Analysis of PPME-1 mRNA expression from TCGA dataset of colon and rectal adenocarcinoma (COADREAD) patient cohort confirmed high PPME1 expression as an independent protective factor predicting favorable overall survival (OS) (P = 0.005, n = 396) compared to patients with low PPME1 expression. CRC cell lines were used to study the effect of PME-1 knockdown by siRNA on cell survival. Contrary to other cancer types, PME-1 inhibition in CRC cell lines did not reduce the viability of cells or the expression of active phosphorylated AKT and ERK proteins. In conclusion, PME-1 expression predicts for a favorable outcome of CRC patients. The unexpected role of PME-1 in CRC in contrast with the oncogenic role of PP2A inhibitor proteins in other malignancies warrants further studies of cancer-specific function for each of these proteins.
authors.affiliation: Department of Pathology, University of Turku, Turku, 20520, Finland.|Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, 20520, Finland.|TuBS and TuDMM Doctoral Programmes, Turku, 20520, Finland.
authors.forename: Amanpreet
authors.initials: A
authors.lastname: Kaur
authors.affiliation: Department of Pathology, University of Turku, Turku, 20520, Finland.|Department of Pathology, Faculty of Medicine, Benghazi University, PO Box 1308, Benghazi, Libya.|Biotechnology Research Center, Tripoli, Libya.
authors.forename: Adam
authors.initials: A
authors.lastname: Elzagheid
authors.affiliation: Department of Pathology, University of Turku, Turku, 20520, Finland.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Birkman
authors.affiliation: Department of Pathology, University of Turku, Turku, 20520, Finland.|Department of Oncology and Radiotherapy, University of Turku and Turku University Hospital, Turku, 20521, Finland.|Department of Social Services and Healthcare, City of Helsinki, Helsinki, 00099, Finland.
authors.forename: Tuulia
authors.initials: T
authors.lastname: Avoranta
authors.affiliation: BioMediTech, University of Tampere, Tampere, 33520, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Kytölä
authors.affiliation: Department of Oncology and Radiotherapy, University of Turku and Turku University Hospital, Turku, 20521, Finland.
authors.forename: Eija
authors.initials: E
authors.lastname: Korkeila
authors.affiliation: Department of Clinical Research, Biohit Oyj, Helsinki, 00880, Finland.|Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, 14784-400, Brazil.
authors.forename: Kari
authors.initials: K
authors.lastname: Syrjänen
authors.affiliation: Department of Pathology, University of Turku, Turku, 20520, Finland.|Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, 20520, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Westermarck
authors.affiliation: Department of Pathology, University of Turku, Turku, 20520, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Sundström
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D002265:Carboxylic Ester Hydrolases / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D063868:Patient Outcome Assessment; D011379:Prognosis; D016016:Proportional Hazards Models; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; D002265:Carboxylic Ester Hydrolases; C119357:protein phosphatase methylesterase-1
keywords: Biomarker; PME-1; PP2A; TCGA; colorectal cancer; survival