Translational Research and Biomarkers

Annals of Surgical Oncology

, Volume 19, Issue 11, pp 3627-3635

First online:

FANCJ Expression Predicts the Response to 5-Fluorouracil-Based Chemotherapy in MLH1-Proficient Colorectal Cancer

  • Ryota NakanishiAffiliated withDepartment of Molecular Oncology, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
  • , Hiroyuki KitaoAffiliated withDepartment of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University Email author 
  • , Yoshihiko FujinakaAffiliated withDepartment of Molecular Oncology, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
  • , Nami YamashitaAffiliated withDepartment of Molecular Oncology, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
  • , Makoto IimoriAffiliated withDepartment of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University
  • , Eriko TokunagaAffiliated withDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
  • , Natsumi YamashitaAffiliated withDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
  • , Masaru MoritaAffiliated withDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
  • , Yoshihiro KakejiAffiliated withDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
    • , Yoshihiko MaeharaAffiliated withDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University

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Abstract

Purpose

Fanconi anemia protein, FANCJ, directly interacts with MLH1, a key protein involved in DNA mismatch repair. Deficient mismatch repair, or microsatellite instability, is a potent marker for the ineffectiveness of 5-fluorouracil (5-FU) in colorectal cancer (CRC). We investigated the significance of FANCJ expression in CRC, focusing on the effects of 5-FU-based adjuvant chemotherapy.

Methods

Clinicopathologic features and immunohistochemical expression of FANCJ and MLH1 were studied in 219 patients with CRC. We also analyzed 5-FU sensitivity in CRC cell lines with varying levels of FANCJ expression.

Results

FANCJ expression was elevated in tumor tissues compared with normal epithelial tissue. High expression of FANCJ was significantly associated with 5-FU resistance measured by the SDI test (P < 0.05) and poor recurrence-free survival (RFS) (P < 0.05). Among patients with stage II/III tumors who received 5-FU, patients with tumors exhibiting high FANCJ expression had significantly worse RFS than did patients with tumors exhibiting low FANCJ expression (P < 0.01). Among patients who did not receive adjuvant chemotherapy, FANCJ expression was not correlated with RFS (P = 0.76). High FANCJ expression was correlated with 5-FU resistance in tumors with normal MLH1 expression (P < 0.05) but not in tumors not expressing MLH1 (P = 0.9). In vitro, FANCJ overexpression was correlated with 5-FU resistance in MLH1-proficient HCT116 3-6 cells but not in MLH1-deficient HCT116 cells.

Conclusions

FANCJ could be a useful biomarker to predict the response to 5-FU and prognosis of CRC, particularly in tumors with normal MLH1 expression.