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The significance of aberrant CHFR methylation for clinical response to microtubule inhibitors in gastric cancer

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Abstract

Background

We studied the correlations between CHFR (checkpoint with FHA and RING finger) gene methylation and responses to microtubule inhibitors (MI) in gastric cancer.

Methods

We examined 9 gastric cancer cell lines and 46 gastric cancer specimens from patients who underwent surgical resection. Promoter methylation was determined by methylation-specific polymerase chain reaction (MSP). CHFR mRNA expression was estimated by quantitative reverse transcription–PCR. The MI-induced growth inhibition was assayed by a standard MTT method.

Results

CHFR expression was silenced by aberrant promoter methylation in 3 of 9 gastric cancer cell lines. The level of CHFR mRNA expression was closely correlated with IC50 in the MI-treated cells (R = 0.889, P = 0.005). In 46 patients with gastric cancers, 24 (52%) presented aberrant CHFR methylation. Among them, 12 patients had received treatment with MI because of advanced-stage tumor or tumor recurrence after surgery. The responders to the MI treatment were 29% in patients with CHFR methylation and 20% in those without the methylation. However, 6 (86%) of 7 patients with methylated CHFR tumor showed some regression or no progression, whereas 4 (80%) of 5 patients with unmethylated CHFR tumor manifested progressive deterioration.

Conclusions

These observations indicated that CHFR methylation may be a clinically useful approach to predict the responsiveness of gastric cancers to treatment with MI.

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Authors and Affiliations

  1. Department of Surgery, Saga University Faculty of Medicine, Nabeshima 5-1-1, Saga, 849-8501, Japan

    Yasuo Koga, Yoshihiko Kitajima, Atsushi Miyoshi, Ken Sato, Seiji Sato & Kohji Miyazaki

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  1. Yasuo Koga
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  2. Yoshihiko Kitajima
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  3. Atsushi Miyoshi
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  4. Ken Sato
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  5. Seiji Sato
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  6. Kohji Miyazaki
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Koga, Y., Kitajima, Y., Miyoshi, A. et al. The significance of aberrant CHFR methylation for clinical response to microtubule inhibitors in gastric cancer. J Gastroenterol 41, 133–139 (2006). https://doi.org/10.1007/s00535-005-1732-7

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  • DOI: https://doi.org/10.1007/s00535-005-1732-7

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