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Dipeptidyl-Peptidase IV Activity Is Correlated with Colorectal Cancer Prognosis

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journal.pone.0119436.PDF (910.2Kb)
Date
2015-03-19
Author
Larrinaga Embeita, Gorka
Pérez Urzelai, Itxaro
Sanz Echevarría, María Begoña
Beitia San Vicente, Maider
Errarte Yarza, Peio
Fernández Atucha, Ainhoa
Blanco Criado, Lorena
Etxezarraga Zuluaga, María Carmen
Gil Goicouría, Francisco Javier
López Fernández de Villaverde, José Ignacio
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Plos One 10(3) : (2015) // Article ID e0119436
URI
http://hdl.handle.net/10810/18143
Abstract
Background Dipeptidyl-peptidase IV (EC 3.4.14.5) (DPPIV) is a serine peptidase involved in cell differentiation, adhesion, immune modulation and apoptosis, functions that control neoplastic transformation. Previous studies have demonstrated altered expression and activity of tissue and circulating DPPIV in several cancers and proposed its potential usefulness for early diagnosis in colorectal cancer (CRC). Methods and principal findings The activity and mRNA and protein expression of DPPIV was prospectively analyzed in adenocarcinomas, adenomas, uninvolved colorectal mucosa and plasma from 116 CRC patients by fluorimetric, quantitative RT-PCR and immunohistochemical methods. Results were correlated with the most important classic pathological data related to aggressiveness and with 5-year survival rates. Results showed that: 1) mRNA levels and activity of DPPIV increased in colorectal neoplasms (Kruskal-Wallis test, p<0.01); 2) Both adenomas and CRCs displayed positive cytoplasmic immunostaining with luminal membrane reinforcement; 3) Plasmatic DPPIV activity was lower in CRC patients than in healthy subjects (Mann-U test, p<0.01); 4) Plasmatic DPPIV activity was associated with worse overall and disease-free survivals (log-rank p<0.01, Cox analysis p<0.01). Conclusion/significance 1) Up-regulation of DPPIV in colorectal tumors suggests a role for this enzyme in the neoplastic transformation of colorectal tissues. This finding opens the possibility for new therapeutic targets in these patients. 2) Plasmatic DPPIV is an independent prognostic factor in survival of CRC patients. The determination of DPPIV activity levels in the plasma may be a safe, minimally invasive and inexpensive way to define the aggressiveness of CRC in daily practice.
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