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FANCJ expression predicts the response to 5-fluorouracil-based chemotherapy in MLH1-proficient colorectal cancer

Ryota Nakanishi1, Hiroyuki Kitao, Yoshihiko Fujinaka

  • 1Department of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Annals of Surgical Oncology
|April 25, 2012
PubMed
Abstract

Insights

High Fanconi anemia protein J (FANCJ) expression predicts 5-fluorouracil (5-FU) resistance and poor prognosis in colorectal cancer (CRC). FANCJ may serve as a biomarker for predicting 5-FU response, especially in tumors with normal MLH1 expression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Fanconi anemia protein J (FANCJ) interacts with MLH1, a key DNA mismatch repair protein.
  • Deficient DNA mismatch repair (microsatellite instability) predicts 5-fluorouracil (5-FU) resistance in colorectal cancer (CRC).

Purpose of the Study:

  • Investigate the role of FANCJ expression in CRC.
  • Determine the impact of FANCJ on 5-FU-based adjuvant chemotherapy response and patient prognosis.

Main Methods:

  • Analyzed FANCJ and MLH1 expression via immunohistochemistry in 219 CRC patients.
  • Assessed 5-FU sensitivity in CRC cell lines with varying FANCJ levels.

Main Results:

  • Elevated FANCJ expression in CRC tumors compared to normal tissue.
  • High FANCJ expression correlated with 5-FU resistance and poorer recurrence-free survival (RFS).
  • FANCJ predicted 5-FU resistance and worse RFS in stage II/III CRC patients receiving 5-FU, particularly in MLH1-proficient tumors.

Conclusions:

  • FANCJ is a potential biomarker for predicting 5-FU response and prognosis in CRC.
  • FANCJ's predictive value is most significant in colorectal cancers with normal MLH1 expression.

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