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Evaluation of 5-Fluorouracil Metabolic Enzymes as Predictors of Response to Adjuvant Chemotherapy Outcomes in Patients with Stage II/III Colorectal Cancer: A Decision-Curve Analysis

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Abstract

Background

The effectiveness of 5-fluorouracil (5-FU)-based adjuvant chemotherapy is reported in patients with colorectal cancer (CRC), but the usefulness of 5-FU metabolic enzymes as predictive biomarkers of the efficacy of this chemotherapy remains unclear.

Objective

This study aims to verify whether 5-FU metabolic enzymes are predictive biomarkers in the clinical setting of adjuvant chemotherapy for stage II/III CRC.

Methods

In total, 179 patients with stage II/III CRC who were treated at our institute between 2000 and 2010 were enrolled. Messenger RNA (mRNA) expression of major 5-FU metabolic enzymes, namely thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase (TP), orotate phosphoribosyl transferase, and β-actin (control) was evaluated using the Danenberg Tumor Profile method. mRNA expression and other clinicopathological data were investigated with regard to CRC relapse.

Results

A total of 78 patients underwent surgery alone, while 101 underwent adjuvant chemotherapy (5-FU plus leucovorin [LV] or tegafur plus uracil /LV) following surgery. Relapse-free survival was longer and risk of recurrence was lower in association with high TP mRNA expression than in association with low TP mRNA expression in the adjuvant chemotherapy group (hazard ratio 0.66; 95 % confidence interval 0.47–0.92; p = 0.016), but not in the surgery alone group. mRNA expression of no other enzymes was associated with relapse in both groups. In decision-curve analyses, the predictive efficiency of TP mRNA expression plus clinicopathological factors was slightly better than that of clinicopathological factors only.

Conclusions

TP mRNA expression in tumors predicted the effects of adjuvant chemotherapy for stage II/III CRC, although the beneficial effects were marginal.

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Acknowledgments

The authors thank Chisato Saito for her technical support. This study was approved by the Ethical Committee of Keio University.

Conflict of interest

The authors have no conflicts of interest or financial ties to disclose.

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Authors and Affiliations

  1. Department of Surgery, Keio University School of Medicine, Tokyo, Japan

    Kohei Shigeta, Hirotoshi Hasegawa, Koji Okabayashi & Yuko Kitagawa

  2. Department of Digestive Surgery, Kitasato University Kitasato Institute Hospital, 9-1 Shirokane 5-Chome, Minato-ku, Tokyo, 108-8642, Japan

    Yoshiyuki Ishii

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  1. Kohei Shigeta
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Correspondence to Yoshiyuki Ishii.

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Shigeta, K., Ishii, Y., Hasegawa, H. et al. Evaluation of 5-Fluorouracil Metabolic Enzymes as Predictors of Response to Adjuvant Chemotherapy Outcomes in Patients with Stage II/III Colorectal Cancer: A Decision-Curve Analysis. World J Surg 38, 3248–3256 (2014). https://doi.org/10.1007/s00268-014-2738-1

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  • DOI: https://doi.org/10.1007/s00268-014-2738-1

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