Clinical impact of aspartyl aminopeptidase expression and activity in colorectal cancer.
Aspartyl aminopeptidase (ASP; EC 3.4.11.21) is a widely distributed and abundant cytosolic enzyme that regulates bioactive peptides such as angiotensin II. It has been demonstrated that the expression and activity of this enzyme is modified in tissue and serum of patients with several types of cancer. However, the involvement of ASP in the neoplastic development and survival of patients with colorectal cancer (CRC) has not been analyzed to date. The activity and messenger RNA expression of ASP in tumor tissue (n = 71) and plasma (n = 40) of patients with CRC was analyzed prospectively using fluorometric and quantitative real-time polymerase chain reaction methods. Data obtained from tumor tissue were compared with those from the surrounding normal mucosa. Classic pathologic parameters (grade, stage, nodal invasion, distant metastases and perineural, lymphatic, and vascular invasion) were stratified following ASP data and analyzed for 5-year survival. ASP was upregulated in CRC tissues, and greater activity correlated significantly with the absence of lymph node metastases and with better overall survival. Inversely, greater plasmatic ASP activity was associated with worse overall and disease-free survival. Data suggest that ASP is involved in colorectal neoplasia and point to this enzyme as a potential useful diagnostic tool in clinical practice.
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. Electronic address: gorka.larrinaga@ehu.es.
Gorka
G
Larrinaga
Itxaro
I
Perez
Usue
U
Ariz
Begoña
B
Sanz
Maider
M
Beitia
Peio
P
Errarte
Carmen
C
Etxezarraga
M Luz
ML
Candenas
Francisco M
FM
Pinto
José I
JI
López
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019963:Clinical Chemistry Tests; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis / Q000201:enzymology* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D043384:Glutamyl Aminopeptidase / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016019:Survival Analysis; D015854:Up-Regulation
D012333:RNA, Messenger; D043384:Glutamyl Aminopeptidase
ASP; CRC; DFS; OS; PCR; UP; aspartyl aminopeptidase; cDNA; colorectal cancer; complementary DNA; disease-free survival; mRNA; messenger RNA; overall survival; polymerase chain reaction; unit of peptidase