Role of thymidine phosphorylase and orotate phosphoribosyltransferase mRNA expression and its ratio to dihydropyrimidine dehydrogenase in the prognosis and clinicopathological features of patients with pancreatic cancer.
BACKGROUND
Thymidine phosphorylase (TP), orotate phosphoribosyltransferase (OPRT), and dihydropyrimidine dehydrogenase (DPD) are important enzymes related to the metabolism of 5-fluorouracil and its derivatives. In this study, we analyzed the expression of these enzymes and evaluated the association between the expression of these enzymes and clinicopathological features and prognosis in patients with pancreatic cancer.


METHODS
TP, OPRT, and DPD mRNA expressions were detected using a real-time reverse transcriptional-polymerase chain reaction method or by immunohistochemistry, using surgical specimens obtained from 25 patients with pancreatic cancer.


RESULTS
TP mRNA expression was lower in cases with an alpha infiltration growth pattern than in cases with other infiltration growth patterns (P < 0.05). OPRT mRNA expression was higher in poorly differentiated-type cases than in differentiated type cases (P < 0.05). TP-, OPRT-, and DPD-positive stainings were found in 15 of 24 cases (63%), 10 of 19 cases (53%), and 14 of 21 cases (67%), respectively. There were significant correlations or trends between the mRNA and protein expressions of TP, OPRT, and DPD. Patients with a low TP/DPD ratio survived significantly longer than those with a high ratio (P < 0.05). Multivariate analysis demonstrated a significantly poorer outcome in patients with a high TP/DPD ratio compared with in patients with a low ratio (P < 0.05).


CONCLUSIONS
The TP/DPD ratio might be useful as a prognostic factor in patients with pancreatic cancer.
Miyake
Kotaro
K
Department of Digestive and Pediatric Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8503 Japan.
Imura
Satoru
S
Yoshizumi
Tomoharu
T
Ikemoto
Tetsuya
T
Morine
Yuji
Y
Shimada
Mitsuo
M
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D008297:Male; D008875:Middle Aged; D009962:Orotate Phosphoribosyltransferase / Q000187:drug effects / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D016019:Survival Analysis; D013939:Thymidine Phosphorylase / Q000187:drug effects / Q000378:metabolism*; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D003841:Deoxycytidine; D042943:Dihydrouracil Dehydrogenase (NADP); D009962:Orotate Phosphoribosyltransferase; D013939:Thymidine Phosphorylase; D005472:Fluorouracil; D000093542:Gemcitabine