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Cancer Med. 2015 Dec;4(12):1798-808. doi: 10.1002/cam4.541. Epub 2015 Sep 17.

Protein phosphatase methylesterase-1 (PME-1) expression predicts a favorable clinical outcome in colorectal cancer.

Author information

1
Department of Pathology, University of Turku, Turku, 20520, Finland.
2
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, 20520, Finland.
3
TuBS and TuDMM Doctoral Programmes, Turku, 20520, Finland.
4
Department of Pathology, Faculty of Medicine, Benghazi University, PO Box 1308, Benghazi, Libya.
5
Biotechnology Research Center, Tripoli, Libya.
6
Department of Oncology and Radiotherapy, University of Turku and Turku University Hospital, Turku, 20521, Finland.
7
Department of Social Services and Healthcare, City of Helsinki, Helsinki, 00099, Finland.
8
BioMediTech, University of Tampere, Tampere, 33520, Finland.
9
Department of Clinical Research, Biohit Oyj, Helsinki, 00880, Finland.
10
Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, 14784-400, Brazil.

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.

KEYWORDS:

Biomarker; PME-1; PP2A; TCGA; colorectal cancer; survival

PMID:
26377365
PMCID:
PMC5123709
DOI:
10.1002/cam4.541
[Indexed for MEDLINE]
Free PMC Article

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