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Dipeptidyl-peptidase IV activity is correlated with colorectal cancer prognosis.

Larrinaga G, Perez I, Sanz B, Beitia M, Errarte P, Fernández A, Blanco L, Etxezarraga MC, Gil J, López JI - PLoS ONE (2015)

Bottom Line: 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). 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nursing I, School of Nursing, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain; Department of Physiology, Faculty of Medicine and Dentistry,University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain; BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.

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.

No MeSH data available.


Related in: MedlinePlus

ROC curves for plasmatic DPPIV activity and CEA levels.Optimal sensitivity and specificity ratios were observed using the following cut-off value: 165 UP/L for plasmatic DPPIV activity both for OS (A) and DFS (B). A cut-off value of 5 ng/mL for CEA, showed lower sensitivity but higher specificity than DPPIV.
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pone.0119436.g005: ROC curves for plasmatic DPPIV activity and CEA levels.Optimal sensitivity and specificity ratios were observed using the following cut-off value: 165 UP/L for plasmatic DPPIV activity both for OS (A) and DFS (B). A cut-off value of 5 ng/mL for CEA, showed lower sensitivity but higher specificity than DPPIV.

Mentions: In plasma samples ROC curves were performed both for DPPIV activity and carcinoembryonic antigen (CEA) levels. For plasmatic DPPIV activity, 165 UP/L cut-off value showed the most optimal sensitivity and specificity ratios (Se = 64% and Sp = 63% for OS, and Se = 65% and Sp = 58% for DFS) (Fig. 5A and 5B). A cut-off value of 5 ng/mL for CEA, which is known to have a prognostic impact in CRC [34], showed lower sensitivity (44% for OS, and 39% for DFS) but higher specificity (68% for OS, and 64% for DFS) than DPPIV (Fig. 5A and 5B).


Dipeptidyl-peptidase IV activity is correlated with colorectal cancer prognosis.

Larrinaga G, Perez I, Sanz B, Beitia M, Errarte P, Fernández A, Blanco L, Etxezarraga MC, Gil J, López JI - PLoS ONE (2015)

ROC curves for plasmatic DPPIV activity and CEA levels.Optimal sensitivity and specificity ratios were observed using the following cut-off value: 165 UP/L for plasmatic DPPIV activity both for OS (A) and DFS (B). A cut-off value of 5 ng/mL for CEA, showed lower sensitivity but higher specificity than DPPIV.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4366149&req=5

pone.0119436.g005: ROC curves for plasmatic DPPIV activity and CEA levels.Optimal sensitivity and specificity ratios were observed using the following cut-off value: 165 UP/L for plasmatic DPPIV activity both for OS (A) and DFS (B). A cut-off value of 5 ng/mL for CEA, showed lower sensitivity but higher specificity than DPPIV.
Mentions: In plasma samples ROC curves were performed both for DPPIV activity and carcinoembryonic antigen (CEA) levels. For plasmatic DPPIV activity, 165 UP/L cut-off value showed the most optimal sensitivity and specificity ratios (Se = 64% and Sp = 63% for OS, and Se = 65% and Sp = 58% for DFS) (Fig. 5A and 5B). A cut-off value of 5 ng/mL for CEA, which is known to have a prognostic impact in CRC [34], showed lower sensitivity (44% for OS, and 39% for DFS) but higher specificity (68% for OS, and 64% for DFS) than DPPIV (Fig. 5A and 5B).

Bottom Line: 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). 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Nursing I, School of Nursing, University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain; Department of Physiology, Faculty of Medicine and Dentistry,University of the Basque Country (UPV/EHU), Leioa, Bizkaia, Spain; BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.

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.

No MeSH data available.


Related in: MedlinePlus