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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

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Abstract

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).

Conclusion

The TP/DPD ratio might be useful as a prognostic factor in patients with pancreatic cancer.

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Authors and Affiliations

  1. Department of Digestive and Pediatric Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan

    Kotaro Miyake, Satoru Imura, Tomoharu Yoshizumi, Tetsuya Ikemoto, Yuji Morine & Mitsuo Shimada

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  1. Kotaro Miyake
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  2. Satoru Imura
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  3. Tomoharu Yoshizumi
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  4. Tetsuya Ikemoto
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  5. Yuji Morine
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  6. Mitsuo Shimada
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Correspondence to Mitsuo Shimada.

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Miyake, K., Imura, S., Yoshizumi, T. et al. 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. Int J Clin Oncol 12, 111–119 (2007). https://doi.org/10.1007/s10147-006-0634-x

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  • DOI: https://doi.org/10.1007/s10147-006-0634-x

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