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© 2015. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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.

Details

Title
Protein phosphatase methylesterase‐1 ( PME ‐1) expression predicts a favorable clinical outcome in colorectal cancer
Author
Kaur, Amanpreet 1 ; Elzagheid, Adam 2 ; Eva‐Maria Birkman 3 ; Avoranta, Tuulia 4 ; Kytölä, Ville 5 ; Korkeila, Eija 6 ; Syrjänen, Kari 7 ; Westermarck, Jukka 8 ; Sundström, Jari 3 

 Department of Pathology, University of Turku, Turku, Finland; Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; TuBS and TuDMM Doctoral Programmes, Turku, Finland 
 Department of Pathology, University of Turku, Turku, Finland; Department of Pathology, Faculty of Medicine, Benghazi University, Benghazi, Libya; Biotechnology Research Center, Tripoli, Libya 
 Department of Pathology, University of Turku, Turku, Finland 
 Department of Pathology, University of Turku, Turku, Finland; Department of Oncology and Radiotherapy, University of Turku and Turku University Hospital, Turku, Finland; Department of Social Services and Healthcare, City of Helsinki, Helsinki, Finland 
 BioMediTech, University of Tampere, Tampere, Finland 
 Department of Oncology and Radiotherapy, University of Turku and Turku University Hospital, Turku, Finland 
 Department of Clinical Research, Biohit Oyj, Helsinki, Finland; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil 
 Department of Pathology, University of Turku, Turku, Finland; Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland 
Pages
1798-1808
Section
Clinical Cancer Research
Publication year
2015
Publication date
Dec 2015
Publisher
John Wiley & Sons, Inc.
e-ISSN
20457634
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2289739406
Copyright
© 2015. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.