Gene expression of ferredoxin reductase predicts outcome in patients with metastatic colorectal cancer treated by 5-fluorouracil plus leucovorin

Wataru Ichikawa, Akio Ooyama, Etsuko Toda, Yoshikazu Sugimoto, Toshinori Oka, Takehiro Takahashi, Michio Shimizu, Yasutsuna Sasaki, Renzo Hirayama

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Purpose: Ferredoxin reductase (FDXR) is a putative contributor to p53-mediated apoptosis from 5-fluorouracil (5-FU) through the generation of oxidative stress in the mitochondria. However, the influence of FDXR gene expression levels on the outcome of 5-FU chemotherapy has been relatively little studied. The aim of this study is to investigate the association between FDXR gene expressions and the clinical outcome when treated by 5-FU chemotherapy, as well as the correlation of FDXR gene expressions and p53 mutation. Methods: Pre-chemotherapeutic fresh frozen samples of 33 patients with metastatic colorectal cancer, who received bolus 5-FU and leucovorin (LV) as first line chemotherapy, were studied. FDXR gene expression and p53 mutation were evaluated by real-time RT-PCR and direct sequencing, respectively. Results: FDXR gene expression was significantly higher in responding tumors compared with non-responding ones (P=0.0379). Patients with FDXR values above the cutoff value of 13.52 had a statistically longer survival than those with FDXR gene expressions below the cutoff value (P=0.0148). The 9 tumors with wild-type p53 had statistically higher FDXR gene expressions than the 14 tumors with mutant-type p53 which had sequence alterations within the "hot spot" codons, the L2-L3 loops, or frameshift (P=0.0463). Conclusions: FDXR gene expression did not affect clinical outcome in patients with wild-type p53 tumors, whereas, among patients with p53 mutant-type tumors, patients with tumors with low FDXR gene expression had a worse outcome than those with a high FDXR gene expression (P=0.0200). FDXR gene expression, which is regulated at least in part by p53, is associated with both response and survival when metastatic colorectal cancer is treated with 5-FU plus LV. In addition, analysis of p53 mutation combined with FDXR gene expression might be useful in estimating the outcome in 5-FU-treated patients.

Original languageEnglish
Pages (from-to)794-801
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume58
Issue number6
DOIs
Publication statusPublished - 2006 Dec 1
Externally publishedYes

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Keywords

  • 5-FU
  • Colorectal cancer
  • Ferredoxin reductase
  • p53 mutation

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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