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Int J Med Sci 2014; 11(2):199-208. doi:10.7150/ijms.7178 This issue Cite

Research Paper

Prolyl Endopeptidase Activity Is Correlated with Colorectal Cancer Prognosis

Gorka Larrinaga^1,2,6✉, Itxaro Perez^{1,2, 6}, Lorena Blanco^{2, 6}, Begoña Sanz^{2, 6}, Peio Errarte^{2, 6}, Maider Beitia^2,6, María C. Etxezarraga^{3, 6}, Alberto Loizate^{4, 6}, Javier Gil^{2, 6}, Jon Irazusta^{2, 6}, José I. López^{5, 6}

1. Department of Nursing I, School of Nursing, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain;
2. Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain;
3. Department of Anatomic Pathology, Basurto University Hospital, University of the Basque Country (UPV/EHU), Bilbao, Bizkaia, Spain;
4. Department of Surgery, Basurto University Hospital, University of the Basque Country (UPV/EHU), Bilbao, Bizkaia, Spain;
5. Department of Anatomic Pathology, Cruces University Hospital, University of the Basque Country (UPV/EHU), Barakaldo, Bizkaia, Spain;
6. BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.

✉ Corresponding author: Gorka Larrinaga, MD, PhD, Department of Nursing I, University School of Nursing, University of the Basque Country. P.O. Box 699, 48080, Bilbao, Bizkaia, Spain, Fax: +34 94 601 3580, Phone: +34 94 601 8076, email: gorka.larrinagaes. More

Abstract

Background and Objective: Prolyl endopeptidase (PEP) (EC 3.4.21.26) is a serine peptidase involved in differentiation, development and proliferation processes of several tissues. Recent studies have demonstrated the increased expression and activity of this cytosolic enzyme in colorectal cancer (CRC). However, there are no available data about the impact of this peptidase in the biological aggressiveness of this tumor in patient survival.

Methods: The activity of PEP in tissue (n=80) and plasma (n=40) of patients with CRC was prospectively analyzed by fluorimetric methods. Results were correlated with the most important classic pathological data related to aggressiveness, with 5-year survival rates and other clinical variables.

Results: 1) PEP is more active in early phases of CRC; 2) Lower levels of the enzyme in tumors were located in the rectum and this decrease could be related with preoperative chemo-radiotherapy; 3) PEP activity in tissue was higher in patients with better overall and disease-free survival (log-rank p<0.01, Cox analysis p<0.01); 4) Plasmatic PEP activity was significantly higher in CRC patients than in healthy individuals and this was associated with distant metastases and with worse overall and disease-free survivals (log-rank p<0.05, Cox analysis p<0.05).

Conclusions: PEP activity in tissue and plasma from CRC patients is an independent prognostic factor in survival. The determination of PEP activity in the plasma may be a safe, minimally invasive and inexpensive way to define the aggressiveness of CRC in daily practice.

Keywords: Prolyl endopeptidase, PEP, colorectal cancer, prognosis, survival.

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