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

Ryota Nakanishi, Hiroyuki Kitao, Yoshihiko Fujinaka, Nami Yamashita, Makoto Iimori, Eriko Tokunaga, Natsumi Yamashita, Masaru Morita, Yoshihiro Kakeji, Yoshihiko Maehara

研究成果: ジャーナルへの寄稿学術誌査読

15 被引用数 (Scopus)

抄録

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 recurrencefree 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.

本文言語英語
ページ(範囲)3627-3635
ページ数9
ジャーナルAnnals of Surgical Oncology
19
11
DOI
出版ステータス出版済み - 10月 2012

!!!All Science Journal Classification (ASJC) codes

  • 外科
  • 腫瘍学

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